115 results on '"Jae‐Seong Yang"'
Search Results
2. Kinetic compartmentalization by unnatural reaction for itaconate production
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Dae-yeol Ye, Myung Hyun Noh, Jo Hyun Moon, Alfonsina Milito, Minsun Kim, Jeong Wook Lee, Jae-Seong Yang, and Gyoo Yeol Jung
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Science - Abstract
Unlike eukaryotic system, bacterial hosts lack membranous system, which is one of the limitations for efficient metabolic engineering. Here, the authors report a kinetic compartmentalization strategy to increase substrate availability from competitive reactions for the efficient production of itaconate in E. coli.
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- 2022
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3. Synthetic biosensor accelerates evolution by rewiring carbon metabolism toward a specific metabolite
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Joo Yeon Seok, Yong Hee Han, Jae-Seong Yang, Jina Yang, Hyun Gyu Lim, Seong Gyeong Kim, Sang Woo Seo, and Gyoo Yeol Jung
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evolutionary metabolic engineering ,synthetic biology ,biosensor ,selection ,adaptive laboratory evolution ,3-hydroxypropionic acid ,Biology (General) ,QH301-705.5 - Abstract
Summary: Proper carbon flux distribution between cell growth and production of a target compound is important for biochemical production because improper flux reallocation inhibits cell growth, thus adversely affecting production yield. Here, using a synthetic biosensor to couple production of a specific metabolite with cell growth, we spontaneously evolve cells under the selective condition toward the acquisition of genotypes that optimally reallocate cellular resources. Using 3-hydroxypropionic acid (3-HP) production from glycerol in Escherichia coli as a model system, we determine that mutations in the conserved regions of proteins involved in global transcriptional regulation alter the expression of several genes associated with central carbon metabolism. These changes rewire central carbon flux toward the 3-HP production pathway, increasing 3-HP yield and reducing acetate accumulation by alleviating overflow metabolism. Our study provides a perspective on adaptive laboratory evolution (ALE) using synthetic biosensors, thereby supporting future efforts in metabolic pathway optimization.
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- 2021
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4. Vibrio sp. dhg as a platform for the biorefinery of brown macroalgae
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Hyun Gyu Lim, Dong Hun Kwak, Sungwoo Park, Sunghwa Woo, Jae-Seong Yang, Chae Won Kang, Beomhee Kim, Myung Hyun Noh, Sang Woo Seo, and Gyoo Yeol Jung
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Science - Abstract
Brown macroalgae is a good candidate feedstock for biorefinery, but the major carbohydrate alginate cannot be digested by current industrial microbes. Here, the authors isolate Vibrio sp. dhg and engineer it to produce value-added biochemicals from alginate using newly developed genetic tools.
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- 2019
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5. Silencing of SRRM4 suppresses microexon inclusion and promotes tumor growth across cancers.
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Sarah A Head, Xavier Hernandez-Alias, Jae-Seong Yang, Ludovica Ciampi, Violeta Beltran-Sastre, Antonio Torres-Méndez, Manuel Irimia, Martin H Schaefer, and Luis Serrano
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Biology (General) ,QH301-705.5 - Abstract
RNA splicing is widely dysregulated in cancer, frequently due to altered expression or activity of splicing factors (SFs). Microexons are extremely small exons (3-27 nucleotides long) that are highly evolutionarily conserved and play critical roles in promoting neuronal differentiation and development. Inclusion of microexons in mRNA transcripts is mediated by the SF Serine/Arginine Repetitive Matrix 4 (SRRM4), whose expression is largely restricted to neural tissues. However, microexons have been largely overlooked in prior analyses of splicing in cancer, as their small size necessitates specialized computational approaches for their detection. Here, we demonstrate that despite having low expression in normal nonneural tissues, SRRM4 is further silenced in tumors, resulting in the suppression of normal microexon inclusion. Remarkably, SRRM4 is the most consistently silenced SF across all tumor types analyzed, implying a general advantage of microexon down-regulation in cancer independent of its tissue of origin. We show that this silencing is favorable for tumor growth, as decreased SRRM4 expression in tumors is correlated with an increase in mitotic gene expression, and up-regulation of SRRM4 in cancer cell lines dose-dependently inhibits proliferation in vitro and in a mouse xenograft model. Further, this proliferation inhibition is accompanied by induction of neural-like expression and splicing patterns in cancer cells, suggesting that SRRM4 expression shifts the cell state away from proliferation and toward differentiation. We therefore conclude that SRRM4 acts as a proliferation brake, and tumors gain a selective advantage by cutting off this brake.
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- 2021
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6. Impact of C‐terminal amino acid composition on protein expression in bacteria
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Marc Weber, Raul Burgos, Eva Yus, Jae‐Seong Yang, Maria Lluch‐Senar, and Luis Serrano
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bacteria ,bias ,C‐terminal ,degradation ,expression ,Biology (General) ,QH301-705.5 ,Medicine (General) ,R5-920 - Abstract
Abstract The C‐terminal sequence of a protein is involved in processes such as efficiency of translation termination and protein degradation. However, the general relationship between features of this C‐terminal sequence and levels of protein expression remains unknown. Here, we identified C‐terminal amino acid biases that are ubiquitous across the bacterial taxonomy (1,582 genomes). We showed that the frequency is higher for positively charged amino acids (lysine, arginine), while hydrophobic amino acids and threonine are lower. We then studied the impact of C‐terminal composition on protein levels in a library of Mycoplasma pneumoniae mutants, covering all possible combinations of the two last codons. We found that charged and polar residues, in particular lysine, led to higher expression, while hydrophobic and aromatic residues led to lower expression, with a difference in protein levels up to fourfold. We further showed that modulation of protein degradation rate could be one of the main mechanisms driving these differences. Our results demonstrate that the identity of the last amino acids has a strong influence on protein expression levels.
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- 2020
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7. rec-YnH enables simultaneous many-by-many detection of direct protein–protein and protein–RNA interactions
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Jae-Seong Yang, Mireia Garriga-Canut, Nele Link, Carlo Carolis, Katrina Broadbent, Violeta Beltran-Sastre, Luis Serrano, and Sebastian P. Maurer
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Science - Abstract
Current methods to unveil protein–protein and protein–RNA interactions often involve long, costly procedures. Here the authors present a rapid yeast 2- and 3-hybrid screening pipeline to detect interactions within protein libraries or between protein libraries and RNA fragment pools.
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- 2018
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8. A reporter system coupled with high-throughput sequencing unveils key bacterial transcription and translation determinants
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Eva Yus, Jae-Seong Yang, Adrià Sogues, and Luis Serrano
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Science - Abstract
Quantitative analysis of how DNA sequence determines transcription and translation regulation is of interest to systems and synthetic biologists. Here the authors present ELM-seq, which uses Dam activity as reporter for high-throughput analysis of promoter and 5’-UTR regions.
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- 2017
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9. MDT-15/MED15 permits longevity at low temperature via enhancing lipidostasis and proteostasis.
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Dongyeop Lee, Seon Woo A An, Yoonji Jung, Yasuyo Yamaoka, Youngjae Ryu, Grace Ying Shyen Goh, Arshia Beigi, Jae-Seong Yang, Gyoo Yeol Jung, Dengke K Ma, Chang Man Ha, Stefan Taubert, Youngsook Lee, and Seung-Jae V Lee
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Biology (General) ,QH301-705.5 - Abstract
Low temperatures delay aging and promote longevity in many organisms. However, the metabolic and homeostatic aspects of low-temperature-induced longevity remain poorly understood. Here, we show that lipid homeostasis regulated by Caenorhabditis elegans Mediator 15 (MDT-15 or MED15), a transcriptional coregulator, is essential for low-temperature-induced longevity and proteostasis. We find that inhibition of mdt-15 prevents animals from living long at low temperatures. We show that MDT-15 up-regulates fat-7, a fatty acid desaturase that converts saturated fatty acids (SFAs) to unsaturated fatty acids (UFAs), at low temperatures. We then demonstrate that maintaining a high UFA/SFA ratio is essential for proteostasis at low temperatures. We show that dietary supplementation with a monounsaturated fatty acid, oleic acid (OA), substantially mitigates the short life span and proteotoxicity in mdt-15(-) animals at low temperatures. Thus, lipidostasis regulated by MDT-15 appears to be a limiting factor for proteostasis and longevity at low temperatures. Our findings highlight the crucial roles of lipid regulation in maintaining normal organismal physiology under different environmental conditions.
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- 2019
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10. Dissecting the calcium-induced differentiation of human primary keratinocytes stem cells by integrative and structural network analyses.
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Kiana Toufighi, Jae-Seong Yang, Nuno Miguel Luis, Salvador Aznar Benitah, Ben Lehner, Luis Serrano, and Christina Kiel
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Biology (General) ,QH301-705.5 - Abstract
The molecular details underlying the time-dependent assembly of protein complexes in cellular networks, such as those that occur during differentiation, are largely unexplored. Focusing on the calcium-induced differentiation of primary human keratinocytes as a model system for a major cellular reorganization process, we look at the expression of genes whose products are involved in manually-annotated protein complexes. Clustering analyses revealed only moderate co-expression of functionally related proteins during differentiation. However, when we looked at protein complexes, we found that the majority (55%) are composed of non-dynamic and dynamic gene products ('di-chromatic'), 19% are non-dynamic, and 26% only dynamic. Considering three-dimensional protein structures to predict steric interactions, we found that proteins encoded by dynamic genes frequently interact with a common non-dynamic protein in a mutually exclusive fashion. This suggests that during differentiation, complex assemblies may also change through variation in the abundance of proteins that compete for binding to common proteins as found in some cases for paralogous proteins. Considering the example of the TNF-α/NFκB signaling complex, we suggest that the same core complex can guide signals into diverse context-specific outputs by addition of time specific expressed subunits, while keeping other cellular functions constant. Thus, our analysis provides evidence that complex assembly with stable core components and competition could contribute to cell differentiation.
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- 2015
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11. Protein conservation and variation suggest mechanisms of cell type-specific modulation of signaling pathways.
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Martin H Schaefer, Jae-Seong Yang, Luis Serrano, and Christina Kiel
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Biology (General) ,QH301-705.5 - Abstract
Many proteins and signaling pathways are present in most cell types and tissues and yet perform specialized functions. To elucidate mechanisms by which these ubiquitous pathways are modulated, we overlaid information about cross-cell line protein abundance and variability, and evolutionary conservation onto functional pathway components and topological layers in the pathway hierarchy. We found that the input (receptors) and the output (transcription factors) layers evolve more rapidly than proteins in the intermediary transmission layer. In contrast, protein expression variability decreases from the input to the output layer. We observed that the differences in protein variability between the input and transmission layer can be attributed to both the network position and the tendency of variable proteins to physically interact with constitutively expressed proteins. Differences in protein expression variability and conservation are also accompanied by the tendency of conserved and constitutively expressed proteins to acquire somatic mutations, while germline mutations tend to occur in cell type-specific proteins. Thus, conserved core proteins in the transmission layer could perform a fundamental role in most cell types and are therefore less tolerant to germline mutations. In summary, we propose that the core signal transmission machinery is largely modulated by a variable input layer through physical protein interactions. We hypothesize that the bow-tie organization of cellular signaling on the level of protein abundance variability contributes to the specificity of the signal response in different cell types.
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- 2014
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12. Discovery of cellular proteins required for the early steps of HCV infection using integrative genomics.
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Ji Hoon Park, Solip Park, Jae-Seong Yang, Oh Sung Kwon, Sanguk Kim, and Sung Key Jang
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Medicine ,Science - Abstract
Successful viral infection requires intimate communication between virus and host cell, a process that absolutely requires various host proteins. However, current efforts to discover novel host proteins as therapeutic targets for viral infection are difficult. Here, we developed an integrative-genomics approach to predict human genes involved in the early steps of hepatitis C virus (HCV) infection. By integrating HCV and human protein associations, co-expression data, and tight junction-tetraspanin web specific networks, we identified host proteins required for the early steps in HCV infection. Moreover, we validated the roles of newly identified proteins in HCV infection by knocking down their expression using small interfering RNAs. Specifically, a novel host factor CD63 was shown to directly interact with HCV E2 protein. We further demonstrated that an antibody against CD63 blocked HCV infection, indicating that CD63 may serve as a new therapeutic target for HCV-related diseases. The candidate gene list provides a source for identification of new therapeutic targets.
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- 2013
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13. Rewiring of PDZ domain-ligand interaction network contributed to eukaryotic evolution.
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Jinho Kim, Inhae Kim, Jae-Seong Yang, Young-Eun Shin, Jihye Hwang, Solip Park, Yoon Sup Choi, and Sanguk Kim
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Genetics ,QH426-470 - Abstract
PDZ domain-mediated interactions have greatly expanded during metazoan evolution, becoming important for controlling signal flow via the assembly of multiple signaling components. The evolutionary history of PDZ domain-mediated interactions has never been explored at the molecular level. It is of great interest to understand how PDZ domain-ligand interactions emerged and how they become rewired during evolution. Here, we constructed the first human PDZ domain-ligand interaction network (PDZNet) together with binding motif sequences and interaction strengths of ligands. PDZNet includes 1,213 interactions between 97 human PDZ proteins and 591 ligands that connect most PDZ protein-mediated interactions (98%) in a large single network via shared ligands. We examined the rewiring of PDZ domain-ligand interactions throughout eukaryotic evolution by tracing changes in the C-terminal binding motif sequences of the PDZ ligands. We found that interaction rewiring by sequence mutation frequently occurred throughout evolution, largely contributing to the growth of PDZNet. The rewiring of PDZ domain-ligand interactions provided an effective means of functional innovations in nervous system development. Our findings provide empirical evidence for a network evolution model that highlights the rewiring of interactions as a mechanism for the development of new protein functions. PDZNet will be a valuable resource to further characterize the organization of the PDZ domain-mediated signaling proteome.
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- 2012
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14. Rational engineering of enzyme allosteric regulation through sequence evolution analysis.
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Jae-Seong Yang, Sang Woo Seo, Sungho Jang, Gyoo Yeol Jung, and Sanguk Kim
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Biology (General) ,QH301-705.5 - Abstract
Control of enzyme allosteric regulation is required to drive metabolic flux toward desired levels. Although the three-dimensional (3D) structures of many enzyme-ligand complexes are available, it is still difficult to rationally engineer an allosterically regulatable enzyme without decreasing its catalytic activity. Here, we describe an effective strategy to deregulate the allosteric inhibition of enzymes based on the molecular evolution and physicochemical characteristics of allosteric ligand-binding sites. We found that allosteric sites are evolutionarily variable and comprised of more hydrophobic residues than catalytic sites. We applied our findings to design mutations in selected target residues that deregulate the allosteric activity of fructose-1,6-bisphosphatase (FBPase). Specifically, charged amino acids at less conserved positions were substituted with hydrophobic or neutral amino acids with similar sizes. The engineered proteins successfully diminished the allosteric inhibition of E. coli FBPase without affecting its catalytic efficiency. We expect that our method will aid the rational design of enzyme allosteric regulation strategies and facilitate the control of metabolic flux.
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- 2012
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15. Network clustering revealed the systemic alterations of mitochondrial protein expression.
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Jouhyun Jeon, Jae Hoon Jeong, Je-Hyun Baek, Hyun-Jung Koo, Wook-Ha Park, Jae-Seong Yang, Myeong-Hee Yu, Sanguk Kim, and Youngmi Kim Pak
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Biology (General) ,QH301-705.5 - Abstract
The mitochondrial protein repertoire varies depending on the cellular state. Protein component modifications caused by mitochondrial DNA (mtDNA) depletion are related to a wide range of human diseases; however, little is known about how nuclear-encoded mitochondrial proteins (mt proteome) changes under such dysfunctional states. In this study, we investigated the systemic alterations of mtDNA-depleted (ρ(0)) mitochondria by using network analysis of gene expression data. By modularizing the quantified proteomics data into protein functional networks, systemic properties of mitochondrial dysfunction were analyzed. We discovered that up-regulated and down-regulated proteins were organized into two predominant subnetworks that exhibited distinct biological processes. The down-regulated network modules are involved in typical mitochondrial functions, while up-regulated proteins are responsible for mtDNA repair and regulation of mt protein expression and transport. Furthermore, comparisons of proteome and transcriptome data revealed that ρ(0) cells attempted to compensate for mtDNA depletion by modulating the coordinated expression/transport of mt proteins. Our results demonstrate that mt protein composition changed to remodel the functional organization of mitochondrial protein networks in response to dysfunctional cellular states. Human mt protein functional networks provide a framework for understanding how cells respond to mitochondrial dysfunctions.
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- 2011
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16. OASIS: online application for the survival analysis of lifespan assays performed in aging research.
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Jae-Seong Yang, Hyun-Jun Nam, Mihwa Seo, Seong Kyu Han, Yonghwan Choi, Hong Gil Nam, Seung-Jae Lee, and Sanguk Kim
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Medicine ,Science - Abstract
Aging is a fundamental biological process. Characterization of genetic and environmental factors that influence lifespan is a crucial step toward understanding the mechanisms of aging at the organism level. To capture the different effects of genetic and environmental factors on lifespan, appropriate statistical analyses are needed.We developed an online application for survival analysis (OASIS) that helps conduct various novel statistical tasks involved in analyzing survival data in a user-friendly manner. OASIS provides standard survival analysis results including Kaplan-Meier estimates and mean/median survival time by taking censored survival data. OASIS also provides various statistical tests including comparison of mean survival time, overall survival curve, and survival rate at specific time point. To visualize survival data, OASIS generates survival and log cumulative hazard plots that enable researchers to easily interpret their experimental results. Furthermore, we provide statistical methods that can analyze variances among survival datasets. In addition, users can analyze proportional effects of risk factors on survival.OASIS provides a platform that is essential to facilitate efficient statistical analyses of survival data in the field of aging research. Web application and a detailed description of algorithms are accessible from http://sbi.postech.ac.kr/oasis.
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- 2011
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17. Changes in hepatic gene expression upon oral administration of taurine-conjugated ursodeoxycholic acid in ob/ob mice.
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Jae-Seong Yang, Jin Taek Kim, Jouhyun Jeon, Ho Sun Park, Gyeong Hoon Kang, Kyong Soo Park, Hong Kyu Lee, Sanguk Kim, and Young Min Cho
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Medicine ,Science - Abstract
Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and associated with considerable morbidities. Unfortunately, there is no currently available drug established to treat NAFLD. It was recently reported that intraperitoneal administration of taurine-conjugated ursodeoxycholic acid (TUDCA) improved hepatic steatosis in ob/ob mice. We hereby examined the effect of oral TUDCA treatment on hepatic steatosis and associated changes in hepatic gene expression in ob/ob mice. We administered TUDCA to ob/ob mice at a dose of 500 mg/kg twice a day by gastric gavage for 3 weeks. Body weight, glucose homeostasis, endoplasmic reticulum (ER) stress, and hepatic gene expression were examined in comparison with control ob/ob mice and normal littermate C57BL/6J mice. Compared to the control ob/ob mice, TUDCA treated ob/ob mice revealed markedly reduced liver fat stained by oil red O (44.2±5.8% vs. 21.1±10.4%, P
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- 2010
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18. Integration of evolutionary features for the identification of functionally important residues in major facilitator superfamily transporters.
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Jouhyun Jeon, Jae-Seong Yang, and Sanguk Kim
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Biology (General) ,QH301-705.5 - Abstract
The identification of functionally important residues is an important challenge for understanding the molecular mechanisms of proteins. Membrane protein transporters operate two-state allosteric conformational changes using functionally important cooperative residues that mediate long-range communication from the substrate binding site to the translocation pathway. In this study, we identified functionally important cooperative residues of membrane protein transporters by integrating sequence conservation and co-evolutionary information. A newly derived evolutionary feature, the co-evolutionary coupling number, was introduced to measure the connectivity of co-evolving residue pairs and was integrated with the sequence conservation score. We tested this method on three Major Facilitator Superfamily (MFS) transporters, LacY, GlpT, and EmrD. MFS transporters are an important family of membrane protein transporters, which utilize diverse substrates, catalyze different modes of transport using unique combinations of functional residues, and have enough characterized functional residues to validate the performance of our method. We found that the conserved cores of evolutionarily coupled residues are involved in specific substrate recognition and translocation of MFS transporters. Furthermore, a subset of the residues forms an interaction network connecting functional sites in the protein structure. We also confirmed that our method is effective on other membrane protein transporters. Our results provide insight into the location of functional residues important for the molecular mechanisms of membrane protein transporters.
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- 2009
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19. Role of amphipathic helix of a herpesviral protein in membrane deformation and T cell receptor downregulation.
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Chan-Ki Min, Sun-Young Bang, Bon-A Cho, Yun-Hui Choi, Jae-Seong Yang, Sun-Hwa Lee, Seung-Yong Seong, Ki Woo Kim, Sanguk Kim, Jae Ung Jung, Myung-Sik Choi, Ik-Sang Kim, and Nam-Hyuk Cho
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Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Abstract
Lipid rafts are membrane microdomains that function as platforms for signal transduction and membrane trafficking. Tyrosine kinase interacting protein (Tip) of T lymphotropic Herpesvirus saimiri (HVS) is targeted to lipid rafts in T cells and downregulates TCR and CD4 surface expression. Here, we report that the membrane-proximal amphipathic helix preceding Tip's transmembrane (TM) domain mediates lipid raft localization and membrane deformation. In turn, this motif directs Tip's lysosomal trafficking and selective TCR downregulation. The amphipathic helix binds to the negatively charged lipids and induces liposome tubulation, the TM domain mediates oligomerization, and cooperation of the membrane-proximal helix with the TM domain is sufficient for localization to lipid rafts and lysosomal compartments, especially the mutivesicular bodies. These findings suggest that the membrane-proximal amphipathic helix and TM domain provide HVS Tip with the unique ability to deform the cellular membranes in lipid rafts and to downregulate TCRs potentially through MVB formation.
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- 2008
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20. Challenges and advances towards the rational design of microalgal synthetic promoters in Chlamydomonas reinhardtii
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Alfonsina Milito, Moritz Aschern, Josie L McQuillan, and Jae-Seong Yang
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Physiology ,Plant Science - Abstract
Microalgae hold enormous potential to provide a safe and sustainable source of high-value compounds, acting as carbon-fixing biofactories that could help to mitigate rapidly progressing climate change. Bioengineering microalgal strains will be key to optimizing and modifying their metabolic outputs, and to render them competitive with established industrial biotechnology hosts, such as bacteria or yeast. To achieve this, precise and tuneable control over transgene expression will be essential, which would require the development and rational design of synthetic promoters as a key strategy. Among green microalgae, Chlamydomonas reinhardtii represents the reference species for bioengineering and synthetic biology; however, the repertoire of functional synthetic promoters for this species, and for microalgae generally, is limited in comparison to other commercial chassis, emphasizing the need to expand the current microalgal gene expression toolbox. Here, we discuss state-of-the-art promoter analyses, and highlight areas of research required to advance synthetic promoter development in C. reinhardtii. In particular, we exemplify high-throughput studies performed in other model systems that could be applicable to microalgae, and propose novel approaches to interrogating algal promoters. We lastly outline the major limitations hindering microalgal promoter development, while providing novel suggestions and perspectives for how to overcome them.
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- 2023
21. OASIS portable: User-friendly offline suite for secure survival analysis.
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Seong Kyu Han, Kwon, Hyunwoo C., Jae-Seong Yang, Sanguk Kim, and V. Lee, Seung-Jae
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Online application for survival analysis (OASIS) and its update, OASIS 2, have been widely used for survival analysis in biological and medical sciences. Here, we provide a portable version of OASIS, an all-in-one offline suite, to facilitate secure survival analysis without uploading the data to online servers. OASIS portable provides a virtualized and isolated instance of the OASIS 2 webserver, operating on the users' personal computers, and enables user-friendly survival analysis without internet connection and security issues. [ABSTRACT FROM AUTHOR]
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- 2024
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22. Riboswitch-guided chalcone synthase engineering and metabolic flux optimization for enhanced production of flavonoids
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Hyun Gyu Hwang, Alfonsina Milito, Jae-Seong Yang, Sungho Jang, and Gyoo Yeol Jung
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Bioengineering ,Applied Microbiology and Biotechnology ,Biotechnology - Abstract
Flavonoids are a group of secondary metabolites from plants that have received attention as high value-added pharmacological substances. Recently, a robust and efficient bioprocess using recombinant microbes has emerged as a promising approach to supply flavonoids. In the flavonoid biosynthetic pathway, the rate of chalcone synthesis, the first committed step, is a major bottleneck. However, chalcone synthase (CHS) engineering was difficult because of high-level conservation and the absence of effective screening tools, which are limited to overexpression or homolog-based combinatorial strategies. Furthermore, it is necessary to precisely regulate the metabolic flux for the optimum availability of malonyl-CoA, a substrate of chalcone synthesis. In this study, we engineered CHS and optimized malonyl-CoA availability to establish a platform strain for naringenin production, a key molecular scaffold for various flavonoids. First, we engineered CHS through synthetic riboswitch-based high-throughput screening of rationally designed mutant libraries. Consequently, the catalytic efficiency (k
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- 2022
23. Lipid-Oriented Live-Cell Distinction of B and T Lymphocytes
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Young-Tae Chang, Stuart N. Berry, Jae Won Lee, Justin Kok Soon Tan, Yun-Kyu Choi, Kangkyun Baek, Solip Park, Jae-Seong Yang, Gun Tae Jung, Kwang Pyo Kim, Soohyun Park, H. W. Lee, Haw-Young Kwon, Sangho Kim, Ki Hean Kim, Raj Kumar Das, Kyeng Min Park, Kimoon Kim, Sun Hyeok Lee, Nam-Young Kang, National Research Foundation of Korea, Government of South Korea, Institute for Basic Science (South Korea), Pohang University of Science and Technology, and Ministry of Education (South Korea)
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Cell type ,T-Lymphocytes ,Cell ,Bone Marrow Cells ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Catalysis ,Cell membrane ,Mice ,Colloid and Surface Chemistry ,medicine ,Animals ,Progenitor cell ,Fluorescent Dyes ,B-Lymphocytes ,biology ,Chemistry ,Cell Membrane ,Lymphocyte differentiation ,Cell Differentiation ,General Chemistry ,Complex cell ,Flow Cytometry ,0104 chemical sciences ,Cell biology ,Multicellular organism ,medicine.anatomical_structure ,Lipidomics ,biology.protein ,Antibody - Abstract
The identification of each cell type is essential for understanding multicellular communities. Antibodies set as biomarkers have been the main toolbox for cell-type recognition, and chemical probes are emerging surrogates. Herein we report the first small-molecule probe, CDgB, to discriminate B lymphocytes from T lymphocytes, which was previously impossible without the help of antibodies. Through the study of the origin of cell specificity, we discovered an unexpected novel mechanism of membrane-oriented live-cell distinction. B cells maintain higher flexibility in their cell membrane than T cells and accumulate the lipid-like probe CDgB more preferably. Because B and T cells share common ancestors, we tracked the cell membrane changes of the progenitor cells and disclosed the dynamic reorganization of the membrane properties over the lymphocyte differentiation progress. This study casts an orthogonal strategy for the small-molecule cell identifier and enriches the toolbox for live-cell distinction from complex cell communities., This research was supported by the Institute for Basic Science (IBS) (IBS-R007-A1), the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (no. 2020R1A2C2009776), the Ministry of Education (no. 2020R1A6A1A03047902), and the intramural fund of POSTECH (Pohang University of Science and Technology).
- Published
- 2021
24. ConPlex: a server for the evolutionary conservation analysis of protein complex structures.
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Yoon Sup Choi, Seong Kyu Han, Jinho Kim, Jae-Seong Yang, Jouhyun Jeon, Sung Ho Ryu, and Sanguk Kim
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- 2010
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25. rec-Y3H screening allows the detection of simultaneous RNA-protein interface mutations
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Maria Gili, Sebastian P. Maurer, Mireia Garriga-Canut, Silvia Speroni, Jae-Seong Yang, Friedrich Preusser, Ministerio de Ciencia, Innovación y Universidades (España), Ministerio de Economía y Competitividad (España), Agencia Estatal de Investigación (España), Generalitat de Catalunya, Ministerio de Educación, Cultura y Deporte (España), and Ministerio de Economía, Industria y Competitividad (España)
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Interface (Java) ,RNA-binding proteins ,RNA-binding protein ,Computational biology ,Matrix-screening ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Protein-RNA interactions ,Mutation screening ,Humans ,Nucleotide ,Molecular Biology ,Peptide sequence ,030304 developmental biology ,chemistry.chemical_classification ,Regulation of gene expression ,0303 health sciences ,Binding Sites ,Rna protein ,030302 biochemistry & molecular biology ,RNA-Binding Proteins ,RNA ,High-Throughput Screening Assays ,Yeast three-hybrid screening ,Gene Expression Regulation ,chemistry ,Mutation - Abstract
In Press., Understanding which proteins and RNAs directly interact is crucial for revealing cellular mechanisms of gene regulation. Efficient methods allowing to detect RNA-protein interactions and dissect the underlying molecular origin for RNA-binding protein (RBP) specificity are in high demand. The recently developed recombination-Y3H screening (rec-Y3H) enabled many-by-many detection of interactions between pools of proteins and RNA fragments for the first time. Here, we test different conditions for protein-RNA interaction selection during rec-Y3H screening and provide information on the screen performance in several selection media. We further show that rec-Y3H can detect the nucleotide and amino acid sequence determinants of protein-RNA interactions by mutating residues of interacting proteins and RNAs simultaneously. We envision that systematic RNA-protein interface mutation screening will be useful to understand the molecular origin of RBP selectivity and to engineer RBPs with targeted specificities in the future., This work was funded by the Spanish Ministry of Economy and Competitiveness (MINECO) [BFU2017-85361-P] and the National Research Foundation of Korea (NRF) funded by the Ministry of Education [2018R1A6A3A11045727]. We further acknowledge support of the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) to the EMBL partnership, the ‘Centro de Excelencia Severo Ochoa’ [SEV-2012-0208] and the CERCA Programme/Generalitat de Catalunya.
- Published
- 2020
26. Kinetic compartmentalization by unnatural reaction for itaconate production
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Jae-Seong Yang, Jeong Wook Lee, Jo Hyun Moon, Myung Hyun Noh, Daeyeol Ye, Minsun Kim, Gyoo Yeol Jung, Alfonsina Milito, National Research Foundation of Korea, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Generalitat de Catalunya, and European Commission
- Subjects
Multidisciplinary ,Chemistry ,General Physics and Astronomy ,Succinates ,General Chemistry ,Compartmentalization (psychology) ,General Biochemistry, Genetics and Molecular Biology ,Applied microbiology ,Metabolic Engineering ,Escherichia coli ,Biophysics ,Metabolic engineering ,Metabolic Networks and Pathways ,Synthetic biology - Abstract
Physical compartmentalization of metabolism using membranous organelles in eukaryotes is helpful for chemical biosynthesis to ensure the availability of substrates from competitive metabolic reactions. Bacterial hosts lack such a membranous system, which is one of the major limitations for efficient metabolic engineering. Here, we employ kinetic compartmentalization with the introduction of an unnatural enzymatic reaction by an engineered enzyme as an alternative strategy to enable substrate availability from competitive reactions through kinetic isolation of metabolic pathways. As a proof of concept, we kinetically isolate the itaconate synthetic pathway from the tricarboxylic acid cycle in Escherichia coli, which is natively separated by mitochondrial membranes in Aspergillus terreus. Specifically, 2-methylcitrate dehydratase is engineered to alternatively catalyze citrate and kinetically secure cis-aconitate for efficient production using a high-throughput screening system. Itaconate production can be significantly improved with kinetic compartmentalization and its strategy has the potential to be widely applicable., This research was supported by the C1 Gas Refinery Program (NRF-2018M3D3A1A01055754, G.Y.J.) and the grants (NRF-2019R1A2C2084631, G.Y.J. and NRF-2021R1A6A3A03043982, M.H.N.) from the National Research Foundation (NRF) of Korea. We also acknowledge that this work was supported by grants SEV‐2015‐0533 and CEX2019-000902-S funded by MCIN/AEI/10.13039/501100011033, and by the CERCA Programme / Generalitat de Catalunya (J.-S.Y.). Also, this project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 945043 (A.M.).
- Published
- 2021
27. Synthetic biosensor accelerates evolution by rewiring carbon metabolism toward a specific metabolite
- Author
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Seong Gyeong Kim, Sang Woo Seo, Hyun Gyu Lim, Jae-Seong Yang, Joo Yeon Seok, Gyoo Yeol Jung, Yong Hee Han, Jina Yang, National Research Foundation of Korea, Ministry of Science, ICT and Future Planning (South Korea), and Seoul National University
- Subjects
Glycerol ,QH301-705.5 ,Metabolite ,selection ,Biosensing Techniques ,3-Hydroxypropionic acid ,biosensor ,General Biochemistry, Genetics and Molecular Biology ,evolutionary metabolic engineering ,chemistry.chemical_compound ,Synthetic biology ,Transcriptional regulation ,Escherichia coli ,Lactic Acid ,Biology (General) ,Overflow metabolism ,adaptive laboratory evolution ,Cell growth ,Escherichia coli Proteins ,Evolutionary metabolic engineering ,Gene Expression Regulation, Bacterial ,Cell biology ,Metabolic pathway ,3-hydroxypropionic acid ,Biosensors ,chemistry ,Metabolic Engineering ,Mutation ,Carbohydrate Metabolism ,synthetic biology ,Directed Molecular Evolution ,Adaptive laboratory evolution ,Flux (metabolism) ,Metabolic Networks and Pathways - Abstract
Proper carbon flux distribution between cell growth and production of a target compound is important for biochemical production because improper flux reallocation inhibits cell growth, thus adversely affecting production yield. Here, using a synthetic biosensor to couple production of a specific metabolite with cell growth, we spontaneously evolve cells under the selective condition toward the acquisition of genotypes that optimally reallocate cellular resources. Using 3-hydroxypropionic acid (3-HP) production from glycerol in Escherichia coli as a model system, we determine that mutations in the conserved regions of proteins involved in global transcriptional regulation alter the expression of several genes associated with central carbon metabolism. These changes rewire central carbon flux toward the 3-HP production pathway, increasing 3-HP yield and reducing acetate accumulation by alleviating overflow metabolism. Our study provides a perspective on adaptive laboratory evolution (ALE) using synthetic biosensors, thereby supporting future efforts in metabolic pathway optimization., This research was supported by the C1 Gas Refinery Program (NRF-2018M3D3A1A01055754 and NRF-2015M3D3A1A01064882), the Global Research Laboratory Program (NRF-2016K1A1A2912829), and the Bio & Medical Technology Development Program (NRF-2018M3A9H3020459) through the National Research Foundation of Korea (NRF of Korea), funded by the Ministry of Science and ICT (MSIT). S.W.S. is partially supported by the Creative-Pioneering Researchers Program through Seoul National University (SNU).
- Published
- 2021
28. Silencing of SRRM4 suppresses microexon inclusion and promotes tumor growth across cancers
- Author
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Manuel Irimia, Violeta Beltran-Sastre, Luis Serrano, Xavier Hernandez-Alias, Martin Schaefer, Ludovica Ciampi, Jae-Seong Yang, Antonio Torres-Méndez, Sarah A. Head, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, Fundación Ramón Areces, Ministerio de Economía y Competitividad (España), Generalitat de Catalunya, and Ministerio de Economía, Industria y Competitividad (España)
- Subjects
0301 basic medicine ,Male ,Molecular biology ,Lung and Intrathoracic Tumors ,Exon ,Mice ,0302 clinical medicine ,Sequencing techniques ,Neoplasms ,Gene expression ,Breast Tumors ,Medicine and Health Sciences ,Biology (General) ,10. No inequality ,Càncer ,General Neuroscience ,Prostate Cancer ,Prostate Diseases ,Cell Differentiation ,RNA sequencing ,Exons ,3. Good health ,Cell biology ,Gene Expression Regulation, Neoplastic ,Oncology ,030220 oncology & carcinogenesis ,RNA splicing ,Heterografts ,Female ,General Agricultural and Biological Sciences ,Neuronal Differentiation ,Research Article ,QH301-705.5 ,Urology ,RNA Splicing ,Nerve Tissue Proteins ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Cell Line ,03 medical and health sciences ,Malignant Tumors ,Breast Cancer ,medicine ,Gene silencing ,Animals ,Humans ,Mitosis ,Tumors ,Colorectal Cancer ,Messenger RNA ,General Immunology and Microbiology ,Cancer ,Cancers and Neoplasms ,Biology and Life Sciences ,medicine.disease ,Research and analysis methods ,Genitourinary Tract Tumors ,Alternative Splicing ,030104 developmental biology ,Molecular biology techniques ,Cancer cell ,Genètica ,Developmental Biology - Abstract
RNA splicing is widely dysregulated in cancer, frequently due to altered expression or activity of splicing factors (SFs). Microexons are extremely small exons (3–27 nucleotides long) that are highly evolutionarily conserved and play critical roles in promoting neuronal differentiation and development. Inclusion of microexons in mRNA transcripts is mediated by the SF Serine/Arginine Repetitive Matrix 4 (SRRM4), whose expression is largely restricted to neural tissues. However, microexons have been largely overlooked in prior analyses of splicing in cancer, as their small size necessitates specialized computational approaches for their detection. Here, we demonstrate that despite having low expression in normal nonneural tissues, SRRM4 is further silenced in tumors, resulting in the suppression of normal microexon inclusion. Remarkably, SRRM4 is the most consistently silenced SF across all tumor types analyzed, implying a general advantage of microexon down-regulation in cancer independent of its tissue of origin. We show that this silencing is favorable for tumor growth, as decreased SRRM4 expression in tumors is correlated with an increase in mitotic gene expression, and up-regulation of SRRM4 in cancer cell lines dose-dependently inhibits proliferation in vitro and in a mouse xenograft model. Further, this proliferation inhibition is accompanied by induction of neural-like expression and splicing patterns in cancer cells, suggesting that SRRM4 expression shifts the cell state away from proliferation and toward differentiation. We therefore conclude that SRRM4 acts as a proliferation brake, and tumors gain a selective advantage by cutting off this brake., This project was funded in part by a grant from the Plan Estatal de Investigación Científica y Técnica y de Innovación to L.S. (PGC2018-101271-B-I00, http://www.ciencia.gob.es). S.A.H. is supported by a Marie Skłodowska-Curie Individual Fellowship from the European Union’s Horizon 2020 research and innovation programme (MSCA-IF-2017-794629, http://ec.europa.eu/). X.H. is supported by a PhD fellowship from the Fundación Ramón Areces (http://www.fundacionareces.es). We acknowledge the support of the Spanish Ministry of Economy and Competitiveness, ‘Centro de Excelencia Severo Ochoa’, the CERCA Programme / Generalitat de Catalunya, and the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) to the EMBL partnership.
- Published
- 2021
29. Matrix-screening reveals a vast potential for direct protein-protein interactions among RNA binding proteins
- Author
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Jae-Seong Yang, Silvia Speroni, Mireia Garriga-Canut, Gian Gaetano Tartaglia, Moritz Aschern, Sebastian P. Maurer, Tobias Hoffmann, Benjamin Lang, Maria Gili, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Ministerio de Economía y Competitividad (España), European Commission, and Generalitat de Catalunya
- Subjects
AcademicSubjects/SCI00010 ,rec-Y2H matrix ,RNA-binding protein ,Plasma protein binding ,Computational biology ,Data Resources and Analyses ,Biology ,medicine.disease_cause ,Protein–protein interaction ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Neoplasms ,Two-Hybrid System Techniques ,Genetics ,medicine ,mammalian RBPs ,Animals ,Humans ,RNA, Messenger ,Nucleotide Motifs ,030304 developmental biology ,Regulation of gene expression ,0303 health sciences ,Mutation ,RBPs ,RNA ,RNA-Binding Proteins ,gene regulation ,RNA splicing ,RNA Splicing Factors ,Sequence motif ,030217 neurology & neurosurgery ,Protein Binding - Abstract
RNA-binding proteins (RBPs) are crucial factors of post-transcriptional gene regulation and their modes of action are intensely investigated. At the center of attention are RNA motifs that guide where RBPs bind. However, sequence motifs are often poor predictors of RBP-RNA interactions in vivo. It is hence believed that many RBPs recognize RNAs as complexes, to increase specificity and regulatory possibilities. To probe the potential for complex formation among RBPs, we assembled a library of 978 mammalian RBPs and used rec-Y2H matrix screening to detect direct interactions between RBPs, sampling > 600 K interactions. We discovered 1994 new interactions and demonstrate that interacting RBPs bind RNAs adjacently in vivo. We further find that the mRNA binding region and motif preferences of RBPs deviate, depending on their adjacently binding interaction partners. Finally, we reveal novel RBP interaction networks among major RNA processing steps and show that splicing impairing RBP mutations observed in cancer rewire spliceosomal interaction networks. The dataset we provide will be a valuable resource for understanding the combinatorial interactions of RBPs with RNAs and the resulting regulatory outcomes., Spanish Ministry of Economy and Competitiveness (MINECO) [BFU2017-85361-P, BFU2014-54278-P, BFU2015-62550-ERC]; Spanish Ministry of Economy and Competitiveness to the EMBL partnership, ‘Centro de Excelencia Severo Ochoa’ [SEV-2012–0208 and SEV‐2015‐0533]; Spanish Ministry of Science and Innovation-State Research Agency (AEI), through the ‘Severo Ochoa Programme for Centres of Excellence in R&D’ [SEV-2015-0533 and CEX2019-000902-S]; CERCA Programme/Generalitat de Catalunya; European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie [793135 to B.L.]. Funding for open access charge: Ministerio de Economía y Competitividad.
- Published
- 2021
30. TAPAS: tools to assist the targeted protein quantification of human alternative splice variants.
- Author
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Jae-Seong Yang, Eduard Sabidó, Luis Serrano, and Christina Kiel
- Published
- 2014
- Full Text
- View/download PDF
31. Circuit-guided population acclimation of a synthetic microbial consortium for improved biochemical production
- Author
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Chae Won Kang, Hyun Gyu Lim, Jaehyuk Won, Sanghak Cha, Giyoung Shin, Jae-Seong Yang, Jaeyoung Sung, Gyoo Yeol Jung, and National Research Foundation of Korea
- Subjects
Multidisciplinary ,Alginates ,Acclimatization ,Microbial Consortia ,Escherichia coli ,General Physics and Astronomy ,Ampicillin ,General Chemistry ,General Biochemistry, Genetics and Molecular Biology - Abstract
Microbial consortia have been considered potential platforms for bioprocessing applications. However, the complexity in process control owing to the use of multiple strains necessitates the use of an efficient population control strategy. Herein, we report circuit-guided synthetic acclimation as a strategy to improve biochemical production by a microbial consortium. We designed a consortium comprising alginate-utilizing Vibrio sp. dhg and 3-hydroxypropionic acid (3-HP)-producing Escherichia coli strains for the direct conversion of alginate to 3-HP. We introduced a genetic circuit, named “Population guider”, in the E. coli strain, which degrades ampicillin only when 3-HP is produced. In the presence of ampicillin as a selection pressure, the consortium was successfully acclimated for increased 3-HP production by 4.3-fold compared to that by a simple co-culturing consortium during a 48-h fermentation. We believe this concept is a useful strategy for the development of robust consortium-based bioprocesses., This research was supported by the C1 Gas Refinery Program [NRF-2018M3D3A1A01055754] and National Research Foundation of Korea grant [NRF-2019R1A2C2084631].
- Published
- 2020
32. rec-Y2H matrix screening reveals a vast potential for direct protein-protein interactions among RNA binding proteins
- Author
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Mireia Garriga-Canut, Maria Gili, Silvia Speroni, Jae-Seong Yang, Benjamin Lang, Gian Gaetano Tartaglia, and Sebastian P. Maurer
- Subjects
Regulation of gene expression ,Rna processing ,Chemistry ,RNA ,RNA-binding protein ,Computational biology ,Matrix (biology) ,Sequence motif ,Protein–protein interaction ,RNA Motifs - Abstract
RNA-binding proteins (RBPs) are crucial factors of post-transcriptional gene regulation and their modes of action are intensely investigated. At the center of attention are RNA motifs that guide where RBPs bind. However, sequence motifs are often poor predictors of RBP-RNA interactions in vivo. It is hence believed that many RBPs recognize RNAs as complexes, to increase specificity and regulatory possibilities. To probe the potential for complex formation among RBPs, we assembled a library of 978 mammalian RBPs and used rec-Y2H screening to detect direct interactions between RBPs, sampling > 600 K interactions. We discovered 1994 new interactions and demonstrate that interacting RBPs bind RNAs adjacently in vivo. We further find that the mRNA binding region and motif preferences of RBPs can deviate, depending on their adjacently binding interaction partners. Finally, we reveal novel RBP interaction networks among major RNA processing steps and show that splicing impairing RBP mutations observed in cancer rewire spliceosomal interaction networks.Graphical abstract
- Published
- 2020
33. Erratum to 'Tetrahydrobiopterin enhances mitochondrial biogenesis and cardiac contractility via stimulation of PGC1α signaling' [Volume 1865, Issue 11, 1 November 2019, 165524]
- Author
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Hyoung Kyu Kim, Jouhyun Jeon, In-Sung Song, Hae Jin Heo, Seung Hun Jeong, Le Thanh Long, Vu Thi Thu, Tae Hee Ko, Min Kim, Nari Kim, Sung Ryul Lee, Jae-Seong Yang, Mi Seon Kang, Jung-Mo Ahn, Je-Yoel Cho, Kyung Soo Ko, Byoung Doo Rhee, Bernd Nilius, Nam-Chul Ha, Ippei Shimizu, Tohru Minamino, Kyoung Im Cho, Young Shik Park, Sanguk Kim, and Jin Han
- Subjects
Molecular Medicine ,Molecular Biology - Published
- 2019
34. SAPIN: A framework for the structural analysis of protein interaction networks.
- Author
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Jae-Seong Yang, Anne Campagna, Javier Delgado Blanco, Peter Vanhee, Luis Serrano, and Christina Kiel
- Published
- 2012
- Full Text
- View/download PDF
35. Impact of C-terminal amino acid composition on protein expression in bacteria
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Jae-Seong Yang, Raul Burgos, Maria Lluch-Senar, Luis Serrano, Marc Weber, and Eva Yus
- Subjects
Medicine (General) ,bias ,Arginine ,Lysine ,Mutant ,Bacteris ,0302 clinical medicine ,Cluster Analysis ,Amino Acids ,Biology (General) ,Threonine ,Codon Usage ,bacteria ,Phylogeny ,degradation ,chemistry.chemical_classification ,0303 health sciences ,biology ,Applied Mathematics ,Bacterial taxonomy ,Articles ,Protein Biosynthesis & Quality Control ,Amino acid ,Computational Theory and Mathematics ,Biochemistry ,Codon, Terminator ,General Agricultural and Biological Sciences ,Hydrophobic and Hydrophilic Interactions ,Information Systems ,C‐terminal ,QH301-705.5 ,Protein degradation ,Article ,General Biochemistry, Genetics and Molecular Biology ,Evolution, Molecular ,Amino Acids, Aromatic ,03 medical and health sciences ,Residue (chemistry) ,R5-920 ,Bacterial Proteins ,Protein Domains ,expression ,Amino Acid Sequence ,030304 developmental biology ,General Immunology and Microbiology ,Computational Biology ,biology.organism_classification ,Mycoplasma pneumoniae ,chemistry ,Genes, Bacterial ,Protein Processing, Post-Translational ,Proteïnes ,030217 neurology & neurosurgery ,Bacteria - Abstract
The C‐terminal sequence of a protein is involved in processes such as efficiency of translation termination and protein degradation. However, the general relationship between features of this C‐terminal sequence and levels of protein expression remains unknown. Here, we identified C‐terminal amino acid biases that are ubiquitous across the bacterial taxonomy (1,582 genomes). We showed that the frequency is higher for positively charged amino acids (lysine, arginine), while hydrophobic amino acids and threonine are lower. We then studied the impact of C‐terminal composition on protein levels in a library of Mycoplasma pneumoniae mutants, covering all possible combinations of the two last codons. We found that charged and polar residues, in particular lysine, led to higher expression, while hydrophobic and aromatic residues led to lower expression, with a difference in protein levels up to fourfold. We further showed that modulation of protein degradation rate could be one of the main mechanisms driving these differences. Our results demonstrate that the identity of the last amino acids has a strong influence on protein expression levels., Large‐scale genomics analyses combined with high‐throughput experimental assays reveal that the C‐terminal amino acid composition has a strong influence on protein expression levels in bacteria.
- Published
- 2019
36. Tetrahydrobiopterin enhances mitochondrial biogenesis and cardiac contractility via stimulation of PGC1α signaling
- Author
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Ippei Shimizu, Jung-Mo Ahn, Jouhyun Jeon, Seung Hun Jeong, Hae Jin Heo, Le Thanh Long, Sanguk Kim, Young Shik Park, Nam-Chul Ha, Kyung Soo Ko, Sung Ryul Lee, Kyoung Im Cho, In-Sung Song, Mi Seon Kang, Jin Han, Tohru Minamino, Byoung Doo Rhee, Min Kim, Jae-Seong Yang, Nari Kim, Vu Thi Thu, Hyoung Kyu Kim, Je-Yoel Cho, Tae Hee Ko, and Bernd Nilius
- Subjects
0301 basic medicine ,Male ,SOD2 ,Oxidative phosphorylation ,030204 cardiovascular system & hematology ,Mitochondria, Heart ,Nitric oxide ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,Animals ,Sepiapterin reductase ,Molecular Biology ,Organelle Biogenesis ,Cardiovascular Agents ,Tetrahydrobiopterin ,TFAM ,Biopterin ,Myocardial Contraction ,Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ,Cell biology ,Mice, Inbred C57BL ,030104 developmental biology ,chemistry ,Mitochondrial biogenesis ,Molecular Medicine ,PPARGC1A ,medicine.drug ,Signal Transduction - Abstract
Tetrahydrobiopterin (BH4) shows therapeutic potential as an endogenous target in cardiovascular diseases. Although it is involved in cardiovascular metabolism and mitochondrial biology, its mechanisms of action are unclear. We investigated how BH4 regulates cardiovascular metabolism using an unbiased multiple proteomics approach with a sepiapterin reductase knock-out (Spr-/-) mouse as a model of BH4 deficiency. Spr-/- mice exhibited a shortened life span, cardiac contractile dysfunction, and morphological changes. Multiple proteomics and systems-based data-integrative analyses showed that BH4 deficiency altered cardiac mitochondrial oxidative phosphorylation. Along with decreased transcription of major mitochondrial biogenesis regulatory genes, including Ppargc1a, Ppara, Esrra, and Tfam, Spr-/- mice exhibited lower mitochondrial mass and severe oxidative phosphorylation defects. Exogenous BH4 supplementation, but not nitric oxide supplementation or inhibition, rescued these cardiac and mitochondrial defects. BH4 supplementation also recovered mRNA and protein levels of PGC1α and its target proteins involved in mitochondrial biogenesis (mtTFA and ERRα), antioxidation (Prx3 and SOD2), and fatty acid utilization (CD36 and CPTI-M) in Spr-/- hearts. These results indicate that BH4-activated transcription of PGC1α regulates cardiac energy metabolism independently of nitric oxide and suggests that BH4 has therapeutic potential for cardiovascular diseases involving mitochondrial dysfunction.
- Published
- 2019
37. Catalytic RNA, ribozyme, and its applications in synthetic biology
- Author
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Gyoo Yeol Jung, Soyeon Park, Jae-Seong Yang, Seung Soo Oh, Hyesung Jo, Byunghwa Kang, National Research Foundation of Korea, Ministry of Science, ICT and Future Planning (South Korea), Government of South Korea, and Ministry of Education (South Korea)
- Subjects
0106 biological sciences ,RNase P ,Bioengineering ,Computational biology ,Splicing ,01 natural sciences ,Applied Microbiology and Biotechnology ,Catalysis ,03 medical and health sciences ,Synthetic biology ,Genome editing ,Ribozyme ,Self-cleavage ,010608 biotechnology ,RNA, Catalytic ,030304 developmental biology ,Catalytic RNA ,0303 health sciences ,biology ,Chemistry ,RNA ,Non-coding RNA ,Catalytic RNAs ,RNA splicing ,biology.protein ,Nucleic Acid Conformation ,Synthetic Biology ,Biotechnology - Abstract
Ribozymes are functional RNA molecules that can catalyze biochemical reactions. Since the discovery of the first catalytic RNA, various functional ribozymes (e.g., self-cleaving ribozymes, splicing ribozymes, RNase P, etc.) have been uncovered, and their structures and mechanisms have been identified. Ribozymes have the advantage of possessing features of “RNA” molecules; hence, they are highly applicable for manipulating various biological systems. To fully employ ribozymes in a broad range of biological applications in synthetic biology, a variety of ribozymes have been developed and engineered. Here, we summarize the main features of ribozymes and the methods used for engineering their functions. We also describe the past and recent efforts towards exploiting ribozymes for effective and novel applications in synthetic biology. Based on studies on their significance in biological applications till date, ribozymes are expected to advance technologies in artificial biological systems., This work was supported by the National Research Foundation of Korea (NRF) grant (NRF-2017R1C1B3012050) and the Global Research Laboratory Program (NRF-2016K1A1A2912829) funded by the Korea government (Ministry of Science and ICT). Also, this research was supported by Basic Science Research Program funded by the Ministry of Education (2018R1A6A3A11045727).
- Published
- 2019
38. A Study on Diversification of Farmland Pension Payment
- Author
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Joo-Ho Sung, Kyung-jin Choi, and Jae-Seong Yang
- Subjects
Pension ,media_common.quotation_subject ,Diversification (finance) ,Financial system ,Business ,Payment ,media_common - Published
- 2015
39. KIN-4/MAST kinase promotes PTEN-mediated longevity of Caenorhabditis elegans via binding through a PDZ domain
- Author
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Sanguk Kim, Eunji Kim, Wooseon Hwang, Joo-Yeon Yoo, Jae-Seong Yang, Seung-Jae Lee, Bo Kyoung Suh, Hyun-Jun Nam, Heehwa G. Son, Seon Woo A. An, Eunseok Choi, Sang Ki Park, Ikue Mori, Youngjae Ryu, Keunhee Seo, Youngran Kim, Shunji Nakano, Nhung Thi-Cam Nguyen, and Chang Man Ha
- Subjects
0301 basic medicine ,Mutant ,PDZ domain ,Longevity ,KIN‐4/MAST kinase ,PDZ Domains ,03 medical and health sciences ,0302 clinical medicine ,PTEN ,Animals ,DAF‐18/PTEN ,PDZ ,Protein kinase A ,Caenorhabditis elegans ,Caenorhabditis elegans Proteins ,Original Paper ,biology ,Kinase ,aging ,PTEN Phosphohydrolase ,Cell Biology ,biology.organism_classification ,insulin/IGF‐1 signaling ,Original Papers ,Cell biology ,030104 developmental biology ,biology.protein ,Signal transduction ,030217 neurology & neurosurgery ,lifespan ,Genetic screen - Abstract
PDZ domain‐containing proteins (PDZ proteins) act as scaffolds for protein–protein interactions and are crucial for a variety of signal transduction processes. However, the role of PDZ proteins in organismal lifespan and aging remains poorly understood. Here, we demonstrate that KIN‐4, a PDZ domain‐containing microtubule‐associated serine‐threonine (MAST) protein kinase, is a key longevity factor acting through binding PTEN phosphatase in Caenorhabditis elegans. Through a targeted genetic screen for PDZ proteins, we find that kin‐4 is required for the long lifespan of daf‐2/insulin/IGF‐1 receptor mutants. We then show that neurons are crucial tissues for the longevity‐promoting role of kin‐4. We find that the PDZ domain of KIN‐4 binds PTEN, a key factor for the longevity of daf‐2 mutants. Moreover, the interaction between KIN‐4 and PTEN is essential for the extended lifespan of daf‐2 mutants. As many aspects of lifespan regulation in C. elegans are evolutionarily conserved, MAST family kinases may regulate aging and/or age‐related diseases in mammals through their interaction with PTEN.
- Published
- 2018
40. March2 is required for head formation by mediating Dishevelled degradation in concert with Dapper1
- Author
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Wonhee Han, Jin-Kwan Han, Sanguk Kim, Seong-Moon Cheong, Gun-Sik Cho, Jae-Seong Yang, Hyeyoon Lee, Youngmu Koo, and Saet-Byeol Jo
- Subjects
0301 basic medicine ,Scaffold protein ,chemistry.chemical_classification ,biology ,Xenopus ,Wnt signaling pathway ,Embryo ,biology.organism_classification ,Cell biology ,Ubiquitin ligase ,Dishevelled ,03 medical and health sciences ,Cytosol ,030104 developmental biology ,Ubiquitin ,chemistry ,biology.protein ,Molecular Biology ,Developmental Biology - Abstract
Dishevelled (Dvl/Dsh) is a key scaffold protein that propagates Wnt signaling essential for embryogenesis and homeostasis. However, whether antagonism of Wnt signaling necessary for vertebrate head formation can be achieved through regulation of Dsh protein stability is unclear. Here we show that membrane-associated RING-CH2 (March2), a RING-type E3 ubiquitin ligase, antagonizes Wnt signaling by regulating the turnover of Dsh protein via ubiquitin-mediated lysosomal degradation in prospective head region of Xenopus. We further found that March2 acquires regional and functional specificities for head formation from the Dsh-interacting protein Dapper1 (Dpr1). Dpr1 stabilizes interaction between March2 and Dsh for mediating ubiquitination and subsequent degradation of Dsh protein only in the dorso-animal region of Xenopus embryo. These results suggest that March2 restricts cytosolic pools of Dsh protein and leads to subsequent limitation of Wnt signaling for the precise vertebrate head development.
- Published
- 2018
41. Lipid-Oriented Live-Cell Distinction of B and T Lymphocytes.
- Author
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Haw-Young Kwon, Das, Raj Kumar, Gun Tae Jung, Hong-Guen Lee, Sun Hyeok Lee, Berry, Stuart N., Kok Soon Tan, Justin, Solip Park, Jae-Seong Yang, Soohyun Park, Kangkyun Baek, Kyeng Min Park, Jae Won Lee, Yun-Kyu Choi, Ki Hean Kim, Sangho Kim, Kwang Pyo Kim, Nam-Young Kang, Kimoon Kim, and Young-Tae Chang
- Published
- 2021
- Full Text
- View/download PDF
42. A reporter system coupled with high-throughput sequencing unveils key bacterial transcription and translation determinants
- Author
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Luis Serrano, Eva Yus, Adrià Sogues, Jae-Seong Yang, Center for Genomic Regulation (CRG-UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), Microbiologie structurale - Structural Microbiology (Microb. Struc. (UMR_3528 / U-Pasteur_5)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institució Catalana de Recerca i Estudis Avançats (ICREA), The project was supported by funds from the Fundación Marcelino Botin and the Spanish Ministerio de Economía y Competitividad (BIO2007-61762). This project was financed by Instituto de Salud Carlos III and co-financed by Federación Española de Enfermedades Raras under grant agreement PI10/01702 and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program, under grant agreement Nos 634942 (MycoSynVac) and 670216 (MYCOCHASSIS). We acknowledge support from the Spanish Ministry of Economy and Competitiveness, Centro de Excelencia Severo Ochoa 2013-2017 and the support given by Juan de la Cierva-Incorporación Program (IJCI‐2014‐22070) to J.S.Y. We also acknowledge the support of the CERCA Program/Generalitat de Catalunya., We acknowledge the staff of the Genomics core facility for their assistance, especially to Jochen Hecht for fruitful discussions on the screening designs. Also, we thank the CRG/UPF Proteomics Unit that is part of the Plataforma de Recursos Biomoleculares y Bioinformáticos (Instituto de Salud Carlos III), supported by grant PT13/0001, We thank Lambert Montava for initial clonings, and Verónica Llorens-Rico and Dr Guillaume Filion for comments on the manuscript. We appreciate all the feedback from the Serrano lab members., European Project: 634942,H2020,H2020-LEIT-BIO-2014-1,MycoSynVac(2015), European Project: 670216,H2020,ERC-2014-ADG,MYCOCHASSIS(2015), Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
0301 basic medicine ,Site-Specific DNA-Methyltransferase (Adenine-Specific) ,Translation ,Transcription, Genetic ,Science ,General Physics and Astronomy ,Systems analysis ,Biology ,Article ,General Biochemistry, Genetics and Molecular Biology ,DNA sequencing ,03 medical and health sciences ,Synthetic biology ,Genes, Reporter ,Bacterial transcription ,Transcription (biology) ,Escherichia coli ,lcsh:Science ,Gene ,2. Zero hunger ,Genetics ,Genome ,Multidisciplinary ,Gene Expression Profiling ,High-Throughput Nucleotide Sequencing ,Promoter ,General Chemistry ,DNA Methylation ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,Mycoplasma pneumoniae ,030104 developmental biology ,Gene Expression Regulation ,Regulatory sequence ,Protein Biosynthesis ,DNA methylation ,lcsh:Q ,Transcription - Abstract
Quantitative analysis of the sequence determinants of transcription and translation regulation is relevant for systems and synthetic biology. To identify these determinants, researchers have developed different methods of screening random libraries using fluorescent reporters or antibiotic resistance genes. Here, we have implemented a generic approach called ELM-seq (expression level monitoring by DNA methylation) that overcomes the technical limitations of such classic reporters. ELM-seq uses DamID (Escherichia coli DNA adenine methylase as a reporter coupled with methylation-sensitive restriction enzyme digestion and high-throughput sequencing) to enable in vivo quantitative analyses of upstream regulatory sequences. Using the genome-reduced bacterium Mycoplasma pneumoniae, we show that ELM-seq has a large dynamic range and causes minimal toxicity. We use ELM-seq to determine key sequences (known and putatively novel) of promoter and untranslated regions that influence transcription and translation efficiency. Applying ELM-seq to other organisms will help us to further understand gene expression and guide synthetic biology., Quantitative analysis of how DNA sequence determines transcription and translation regulation is of interest to systems and synthetic biologists. Here the authors present ELM-seq, which uses Dam activity as reporter for high-throughput analysis of promoter and 5’-UTR regions.
- Published
- 2017
43. MDT-15/MED15 permits longevity at low temperature via enhancing lipidostasis and proteostasis
- Author
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Arshia Beigi, Seung-Jae Lee, Gyoo Yeol Jung, Yasuyo Yamaoka, Dongyeop Lee, Stefan Taubert, Yoonji Jung, Youngjae Ryu, Youngsook Lee, Chang Man Ha, Seon Woo A. An, Dengke K. Ma, Jae-Seong Yang, Grace Y. S. Goh, and Campisi, Judith
- Subjects
Fatty Acid Desaturases ,0301 basic medicine ,Aging ,Nematoda ,Physiology ,Medical and Health Sciences ,Biochemistry ,Body Temperature ,Fats ,chemistry.chemical_compound ,RNA interference ,0302 clinical medicine ,Medicine and Health Sciences ,Homeostasis ,Biology (General) ,media_common ,biology ,General Neuroscience ,Fatty Acids ,Longevity ,Eukaryota ,Animal Models ,Biological Sciences ,Lipids ,Cell biology ,Nucleic acids ,Cold Temperature ,Genetic interference ,Experimental Organism Systems ,Physiological Parameters ,Epigenetics ,General Agricultural and Biological Sciences ,Research Article ,Transcriptional Activation ,QH301-705.5 ,media_common.quotation_subject ,Research and Analysis Methods ,Green Fluorescent Protein ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Model Organisms ,Genetics ,Animals ,Caenorhabditis elegans ,Caenorhabditis elegans Proteins ,Nutrition ,Agricultural and Veterinary Sciences ,General Immunology and Microbiology ,Prevention ,Organisms ,Biology and Life Sciences ,Proteins ,Lipid metabolism ,Metabolism ,Lipid Metabolism ,Invertebrates ,Luminescent Proteins ,Oleic acid ,030104 developmental biology ,Proteostasis ,Fatty acid desaturase ,Proteotoxicity ,chemistry ,Dietary Supplements ,Animal Studies ,Caenorhabditis ,biology.protein ,RNA ,Gene expression ,030217 neurology & neurosurgery ,Developmental Biology ,Oleic Acid ,Transcription Factors - Abstract
Low temperatures delay aging and promote longevity in many organisms. However, the metabolic and homeostatic aspects of low-temperature–induced longevity remain poorly understood. Here, we show that lipid homeostasis regulated by Caenorhabditis elegans Mediator 15 (MDT-15 or MED15), a transcriptional coregulator, is essential for low-temperature–induced longevity and proteostasis. We find that inhibition of mdt-15 prevents animals from living long at low temperatures. We show that MDT-15 up-regulates fat-7, a fatty acid desaturase that converts saturated fatty acids (SFAs) to unsaturated fatty acids (UFAs), at low temperatures. We then demonstrate that maintaining a high UFA/SFA ratio is essential for proteostasis at low temperatures. We show that dietary supplementation with a monounsaturated fatty acid, oleic acid (OA), substantially mitigates the short life span and proteotoxicity in mdt-15(-) animals at low temperatures. Thus, lipidostasis regulated by MDT-15 appears to be a limiting factor for proteostasis and longevity at low temperatures. Our findings highlight the crucial roles of lipid regulation in maintaining normal organismal physiology under different environmental conditions., Low temperatures delay aging and promote longevity in many organisms. This study shows that at low ambient temperatures, Mediator 15, a transcriptional coregulator, allows the nematode Caenorhabditis elegans to live longer by increasing the levels of unsaturated lipids, helping to maintain protein homeostasis.
- Published
- 2019
44. A Study on the Satisfaction of School meals about Elementary, Middle and High School's Students in Jeonbuk Area : An Ordered Probit Analysis
- Author
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Sung-Soo Lim and Jae-Seong Yang
- Subjects
Mathematics education ,Ordered probit ,Psychology - Published
- 2013
45. Head formation requires Dishevelled degradation that is mediated by March2 in concert with Dapper1
- Author
-
Hyeyoon, Lee, Seong-Moon, Cheong, Wonhee, Han, Youngmu, Koo, Saet-Byeol, Jo, Gun-Sik, Cho, Jae-Seong, Yang, Sanguk, Kim, and Jin-Kwan, Han
- Subjects
Reverse Transcriptase Polymerase Chain Reaction ,Ubiquitin-Protein Ligases ,Cell Culture Techniques ,Dishevelled Proteins ,Ubiquitination ,Fluorescent Antibody Technique ,Gene Expression Regulation, Developmental ,Xenopus Proteins ,Wnt Proteins ,Xenopus laevis ,Proteolysis ,Morphogenesis ,Animals ,Head ,In Situ Hybridization ,Signal Transduction - Abstract
Dishevelled (Dvl/Dsh) is a key scaffold protein that propagates Wnt signaling essential for embryogenesis and homeostasis. However, whether the antagonism of Wnt signaling that is necessary for vertebrate head formation can be achieved through regulation of Dsh protein stability is unclear. Here, we show that membrane-associated RING-CH2 (March2), a RING-type E3 ubiquitin ligase, antagonizes Wnt signaling by regulating the turnover of Dsh protein via ubiquitin-mediated lysosomal degradation in the prospective head region of
- Published
- 2016
46. OASIS 2: online application for survival analysis 2 with features for the analysis of maximal lifespan and healthspan in aging research
- Author
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Dongyeop Lee, Sanguk Kim, Donghyo Kim, Seung-Jae Lee, Heetak Lee, Jae-Seong Yang, Heehwa G. Son, and Seong Kyu Han
- Subjects
0301 basic medicine ,Gerontology ,Aging ,Biomedical Research ,Population ,Statistics as Topic ,maximum lifespan ,healthspan ,Machine learning ,computer.software_genre ,Graphical tools ,survival ,Field (computer science) ,03 medical and health sciences ,Feature (machine learning) ,Medicine ,Humans ,Statistical analysis ,web-service ,education ,Survival analysis ,education.field_of_study ,Internet ,business.industry ,Age Factors ,Survival Analysis ,030104 developmental biology ,Oncology ,statistics ,Artificial intelligence ,User interface ,Web service ,business ,computer ,Software ,Research Paper - Abstract
Online application for survival analysis (OASIS) has served as a popular and convenient platform for the statistical analysis of various survival data, particularly in the field of aging research. With the recent advances in the fields of aging research that deal with complex survival data, we noticed a need for updates to the current version of OASIS. Here, we report OASIS 2 (http://sbi.postech.ac.kr/oasis2), which provides extended statistical tools for survival data and an enhanced user interface. In particular, OASIS 2 enables the statistical comparison of maximal lifespans, which is potentially useful for determining key factors that limit the lifespan of a population. Furthermore, OASIS 2 provides statistical and graphical tools that compare values in different conditions and times. That feature is useful for comparing age-associated changes in physiological activities, which can be used as indicators of "healthspan." We believe that OASIS 2 will serve as a standard platform for survival analysis with advanced and user-friendly statistical tools for experimental biologists in the field of aging research.
- Published
- 2016
47. Global Sequence Homology Detection Using Word Conservation Probability
- Author
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Jae-Seong Yang, Dae-Kyum Kim, Sanguk Kim, and Jin-Ho Kim
- Subjects
Comparative genomics ,Smith–Waterman algorithm ,Genetics ,Sequence homology ,Exponential growth ,Protein homology ,Computational biology ,Biology ,Similarity measure ,Genome ,Homology (biology) - Abstract
Protein homology detection is an important issue in comparative genomics. Because of the exponential growth of sequence databases, fast and efficient homology detection tools are urgently needed. Currently, for homology detection, sequence comparison methods using local alignment such as BLAST are generally used as they give a reasonable measure for sequence similarity. However, these methods have drawbacks in offering overall sequence similarity, especially in dealing with eukaryotic genomes that often contain many insertions and duplications on sequences. Also these methods do not provide the explicit models for speciation, thus it is difficult to interpret their similarity measure into homology detection. Here, we present a novel method based on Word Conservation Score (WCS) to address the current limitations of homology detection. Instead of counting each amino acid, we adopted the concept of `Word` to compare sequences. WCS measures overall sequence similarity by comparing word contents, which is much faster than BLAST comparisons. Furthermore, evolutionary distance between homologous sequences could be measured by WCS. Therefore, we expect that sequence comparison with WCS is useful for the multiple-species-comparisons of large genomes. In the performance comparisons on protein structural classifications, our method showed a considerable improvement over BLAST. Our method found bigger micro-syntenic blocks which consist of orthologs with conserved gene order. By testing on various datasets, we showed that WCS gives faster and better overall similarity measure compared to BLAST.
- Published
- 2011
48. Molecular Evolution of Protein Conformational Changes Revealed by a Network of Evolutionarily Coupled Residues
- Author
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Jouhyun Jeon, Hyun-Jun Nam, Jihye Hwang, Jae-Seong Yang, Yoon Sup Choi, and Sanguk Kim
- Subjects
chemistry.chemical_classification ,Protein Folding ,Protein Conformation ,Proteins ,Computational biology ,Protein engineering ,Biology ,Amino acid ,Evolution, Molecular ,Structure-Activity Relationship ,Protein structure ,Biochemistry ,chemistry ,Molecular evolution ,Genetics ,Structure–activity relationship ,Protein folding ,Amino Acid Sequence ,Protein Interaction Maps ,Molecular Biology ,Peptide sequence ,Ecology, Evolution, Behavior and Systematics ,Protein Interaction Map - Abstract
An improved understanding of protein conformational changes has broad implications for elucidating the mechanisms of various biological processes and for the design of protein engineering experiments. Understanding rearrangements of residue interactions is a key component in the challenge of describing structural transitions. Evolutionary properties of protein sequences and structures are extensively studied; however, evolution of protein motions, especially with respect to interaction rearrangements, has yet to be explored. Here, we investigated the relationship between sequence evolution and protein conformational changes and discovered that structural transitions are encoded in amino acid sequences as coevolving residue pairs. Furthermore, we found that highly coevolving residues are clustered in the flexible regions of proteins and facilitate structural transitions by forming and disrupting their interactions cooperatively. Our results provide insight into the evolution of protein conformational changes and help to identify residues important for structural transitions.
- Published
- 2011
49. Evolutionary conservation in multiple faces of protein interaction
- Author
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Sanguk Kim, Jae-Seong Yang, Sung Ho Ryu, Yonghwan Choi, and Yoon Sup Choi
- Subjects
Models, Molecular ,Protein interface ,Protein Conformation ,Proteins ,Computational biology ,Models, Theoretical ,Biology ,Biochemistry ,Protein–protein interaction ,Conserved sequence ,Evolution, Molecular ,Crystallography ,Structural Biology ,Docking (molecular) ,Protein Interaction Networks ,Animals ,Humans ,Surface protein ,Molecular Biology ,Protein Binding - Abstract
Protein interfaces are believed to be evolutionarily more conserved than the rest of the protein surface, but this has not been properly verified using a large protein structural set. Furthermore, recent systematic protein interaction analyses have proved that proteins interacting with many partners have multiple interfaces to connect protein interaction networks, which have never taken into account for conservation analysis of protein interface. Here, we studied the evolutionary conservation of protein interfaces using a large-scale dataset of 2646 protein interfaces with the classification of homodimeric/heterodimeric and obligatory/transient interactions, considering all their known multiple interfaces. We found that protein interfaces were indeed more conserved than noninterface surfaces, and the conservation level of protein interfaces increased when multiple interfaces were properly considered. These findings suggest that conservation analysis should be a good descriptor for protein interface identification and protein-protein interaction predictions. We applied this evolutionary feature to filter docking decoys and found that protein interface conservation worked remarkably well in selecting the near-native structures from the large number of generated docking complexes. Moreover, we discovered that a strong correlation exist between protein interface size and protein interface conservation, which could be a useful filter for the prediction of protein-protein interactions.
- Published
- 2009
50. Construction of Functional Interaction Networks through Consensus Localization Predictions of the Human Proteome
- Author
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Sung Key Jang, Jae-Seong Yang, Solip Park, and Sanguk Kim
- Subjects
Proteomics ,Proteome ,Disease Association ,Computational biology ,Biology ,Machine learning ,computer.software_genre ,Sensitivity and Specificity ,Biochemistry ,Mass Spectrometry ,Functional networks ,Sequence Analysis, Protein ,Protein Interaction Mapping ,Human proteome project ,Humans ,Databases, Protein ,Cell Nucleus ,Protein function ,Models, Statistical ,business.industry ,Computational Biology ,Proteins ,Reproducibility of Results ,A protein ,General Chemistry ,Subcellular localization ,Protein subcellular localization prediction ,Mitochondria ,Artificial intelligence ,business ,computer ,Software ,Subcellular Fractions - Abstract
Characterizing the subcellular localization of a protein provides a key clue for understanding protein function. However, different protein localization prediction programs often deliver conflicting results regarding the localization of the same protein. As the number of available localization prediction programs continues to grow, there is a need for a consensus prediction approach. To address this need, we developed a consensus localization prediction method called ConLoc based on a large-scale, systematic integration of 13 available programs that make predictions for five major subcellular localizations (cytosol, extracellular, mitochondria, nucleus, and plasma membrane). The ability of ConLoc to accurately predict protein localization was substantially better than existing programs. Using ConLoc prediction, we built a localization-guided functional interaction network of the human proteome and mapped known disease associations within this network. We found a high degree of shared disease associations among functionally interacting proteins that are localized to the same cellular compartment. Thus, the use of consensus localization prediction, such as ConLoc, is a new approach for the identification of novel disease associated genes.
- Published
- 2009
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