69 results on '"RNA regulation"'
Search Results
2. Paternal environmental exposure-induced spermatozoal small noncoding RNA alteration meditates the intergenerational epigenetic inheritance of multiple diseases
- Author
-
Gaoli Liang, Azhar Anwar, Huanhuan Hu, Chen-Yu Zhang, Yanbo Wang, and Xin Yin
- Subjects
Male ,Mammals ,Genetics ,Offspring ,Total rna ,Inheritance (genetic algorithm) ,RNA ,Environmental Exposure ,General Medicine ,Environmental exposure ,Biology ,Non-coding RNA ,Spermatozoa ,Epigenesis, Genetic ,Rna regulation ,Pregnancy ,Animals ,Humans ,RNA, Small Untranslated ,Female ,Epigenetics - Abstract
Studies of human and mammalian have revealed that environmental exposure can affect paternal health conditions as well as those of the offspring. However, studies that explore the mechanisms that meditate this transmission are rare. Recently, small noncoding RNAs (sncRNAs) in sperm have seemed crucial to this transmission due to their alteration in sperm in response to environmental exposure, and the methodology of microinjection of isolated total RNA or sncRNAs or synthetically identified sncRNAs gradually lifted the veil of sncRNA regulation during intergenerational inheritance along the male line. Hence, by reviewing relevant literature, this study intends to answer the following research concepts: (1) paternal environmental factors that can be passed on to offspring and are attributed to spermatozoal sncRNAs, (2) potential role of paternal spermatozoal sncRNAs during the intergenerational inheritance process, and (3) the potential mechanism by which spermatozoal sncRNAs meditate intergenerational inheritance. In summary, increased attention highlights the hidden wonder of spermatozoal sncRNAs during intergenerational inheritance. Therefore, in the future, more studies should focus on the origin of RNA alteration, the target of RNA regulation, and how sncRNA regulation during embryonic development can be sustained even in adult offspring.
- Published
- 2021
3. RNA structure probing uncovers RNA structure-dependent biological functions
- Author
-
Chu-Xiao Liu, Xi-Wen Wang, Ling-Ling Chen, and Qiangfeng Cliff Zhang
- Subjects
0303 health sciences ,03 medical and health sciences ,030302 biochemistry & molecular biology ,RNA ,Cell Biology ,Computational biology ,Biology ,Nucleic acid structure ,Molecular Biology ,030304 developmental biology ,Rna regulation - Abstract
RNA molecules fold into complex structures that enable their diverse functions in cells. Recent revolutionary innovations in transcriptome-wide RNA structural probing of living cells have ushered in a new era in understanding RNA functions. Here, we summarize the latest technological advances for probing RNA secondary structures and discuss striking discoveries that have linked RNA regulation and biological processes through interrogation of RNA structures. In particular, we highlight how different long noncoding RNAs form into distinct secondary structures that determine their modes of interactions with protein partners to realize their unique functions. These dynamic structures mediate RNA regulatory functions through altering interactions with proteins and other RNAs. We also outline current methodological hurdles and speculate about future directions for development of the next generation of RNA structure-probing technologies of higher sensitivity and resolution, which could then be applied in increasingly physiologically relevant studies.
- Published
- 2021
4. Challenges in RNA Regulation in Huntington's Disease: Insights from Computational Studies
- Author
-
Oscar Palomino-Hernandez, Giulia Rossetti, and Michael A. Margreiter
- Subjects
0303 health sciences ,010304 chemical physics ,Chemistry ,Computational biology ,General Chemistry ,medicine.disease ,01 natural sciences ,Rna regulation ,03 medical and health sciences ,Huntington's disease ,0103 physical sciences ,ddc:540 ,medicine ,030304 developmental biology - Abstract
Novel therapeutic approaches are being developed to tackle neurodegenerative diseases, due to the lack of efficiency of the known druggable targets. For Huntington's disease, a promising approach is the regulation of the RNA product. This target would allow for a selective and effective inhibition of the toxic effects exerted by the final nucleic product and the coded protein. In this review, the current state of the art of RNA regulation is discussed, with a brief but insightful view on novel plausible targets. After this, an emphasis on successful computational and experimental approaches tailored in modeling and regulating RNA aberrant behavior are extensively presented. Finally, the application and limitations of current computational methods are discussed, and possible avenues for improvement are outlined.
- Published
- 2020
- Full Text
- View/download PDF
5. Musashi-1 promotes stress-induced tumor progression through recruitment of AGO2
- Author
-
Jia Shen, Jennifer L. Hsu, Hsiao Yun Chen, Mong Lien Wang, Mien Chie Hung, Hsin I. Ma, Yi Ping Yang, Liang Ting Lin, Shih Hwa Chiou, Yi Wei Chen, Chung-Hsuan Chen, Ming Teh Chen, Chung Pin Li, Wen-chang Lin, Wei Chao Chang, Benoit Laurent, Pin I. Huang, and Chih-Hung Hsu
- Subjects
Male ,0301 basic medicine ,Untranslated region ,Immunoprecipitation ,Mice, Nude ,Medicine (miscellaneous) ,Nerve Tissue Proteins ,Chromosomal translocation ,Endogeny ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,Neoplasms ,Animals ,Humans ,cancer ,subcellular translocation ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,Mice, Inbred BALB C ,Argonaute 2 ,Chemistry ,Carcinoma ,RNA-Binding Proteins ,Argonaute ,tumor recurrence ,Cytosol ,030104 developmental biology ,Musashi-1 ,Tumor progression ,030220 oncology & carcinogenesis ,Argonaute Proteins ,RNA regulation ,Disease Progression ,Cancer research ,Neoplasm Recurrence, Local ,Cell fractionation ,Research Paper - Abstract
Carcinomatous progression and recurrence are the main therapeutic challenges frequently faced by patients with refractory tumors. However, the underlined molecular mechanism remains obscure. Methods: We found Musashi-1 (MSI1) transported into cytosol under stress condition by confocal microscopy and cell fractionation. Argonaute 2 (AGO2) was then identified as a cytosolic binding partner of MSI1 by Mass Spectrametry, immunoprecipitation, and recombinant protein pull-down assay. We used RNA-IP to determine the MSI1/AGO2 associated regions on downstream target mRNAs. Finally, we overexpressed C-terminus of MSI1 to disrupt endogenous MSI1/AGO2 interaction and confirm it effects on tmor progression. Results: Malignant tumors exhibit elevated level of cytosolic Musashi-1 (MSI1), which translocates into cytosol in response to stress and promote tumor progression. Cytosolic MSI1 forms a complex with AGO2 and stabilize or destabilize its target mRNAs by respectively binding to their 3´ untranslated region or coding domain sequence. Both MSI1 translocation and MSI1/AGO2 binding are essential for promoting tumor progression. Blocking MSI1 shuttling by either chemical inhibition or point mutation attenuates the growth of GBM-xenografts in mice. Importantly, overexpression of the C-terminus of MSI1 disrupts endogenous MSI1/AGO2 interaction and effectively reduces stress-induced tumor progression. Conclusion: Our findings highlight novel molecular functions of MSI1 during stress-induced carcinomatous recurrence, and suggest a new therapeutic strategy for refractory malignancies by targeting MSI1 translocation and its interaction with AGOs.
- Published
- 2020
6. Viral Manipulation of a Mechanoresponsive Signaling Axis Disassembles Processing Bodies
- Author
-
Pauline Douglas, Kristina D. Rinker, Elizabeth L. Castle, Jennifer A. Corcoran, and Carolyn-Ann Robinson
- Subjects
herpesviruses ,processing bodies ,RHOA ,Viral protein ,Virus Replication ,medicine.disease_cause ,Mechanotransduction, Cellular ,actin dynamics ,Viral Proteins ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Kaposi's sarcoma-associated herpesvirus ,Cytoskeleton ,Cell Shape ,Sarcoma, Kaposi ,Molecular Biology ,Actin ,mechanotransduction ,virus-host interactions ,030304 developmental biology ,Ribonucleoprotein ,0303 health sciences ,Host Microbial Interactions ,biology ,Effector ,YAP-Signaling Proteins ,Actomyosin ,Cell Biology ,3. Good health ,Cell biology ,tumorigenesis ,Actin Cytoskeleton ,Cell Transformation, Neoplastic ,Gene Expression Regulation ,030220 oncology & carcinogenesis ,RNA regulation ,Herpesvirus 8, Human ,biology.protein ,Ectopic expression ,YAP ,rhoA GTP-Binding Protein ,Research Article ,Signal Transduction - Abstract
Processing bodies (PBs) are ribonucleoprotein granules important for cytokine mRNA decay that are targeted for disassembly by many viruses. Kaposi’s sarcoma-associated herpesvirus is the etiological agent of the inflammatory endothelial cancer, Kaposi’s sarcoma, and a PB-regulating virus. The virus encodes kaposin B (KapB), which induces actin stress fibers (SFs) and cell spindling as well as PB disassembly. We now show that KapB-mediated PB disassembly requires actin rearrangements, RhoA effectors, and the mechanoresponsive transcription activator, YAP. Moreover, ectopic expression of active YAP or exposure of ECs to mechanical forces caused PB disassembly in the absence of KapB. We propose that the viral protein KapB activates a mechanoresponsive signaling axis and links changes in cell shape and cytoskeletal structures to enhanced inflammatory molecule expression using PB disassembly. Our work implies that cytoskeletal changes in other pathologies may similarly impact the inflammatory environment.
- Published
- 2021
7. Nuclear RNA Regulation by XRN2 and XTBD Family Proteins
- Author
-
Takashi S. Miki and Ilkin Aygün
- Subjects
Cell Nucleus ,Transcription, Genetic ,Physiology ,Chemistry ,Ribosome biogenesis ,RNA ,Cell Biology ,General Medicine ,Subcellular localization ,In vitro ,Rna regulation ,Cell biology ,medicine.anatomical_structure ,Exoribonuclease ,Gene expression ,medicine ,Caenorhabditis elegans Proteins ,Molecular Biology ,Nucleus ,RNA, Nuclear - Abstract
XRN2 is a 5'-to-3' exoribonuclease that is predominantly localized in the nucleus. By degrading or trimming various classes of RNA, XRN2 contributes to essential processes in gene expression such as transcription termination and ribosome biogenesis. Despite limited substrate specificity in vitro, XRN2 targets a specific subset of RNA by interacting with other proteins in cells. Here we review the functions of proteins that have an evolutionarily conserved XRN2-binding domain, XTBD. These proteins modulate activity of XRN2 by stabilizing it, controlling its subcellular localization or recruiting it to specific RNA targets, and thereby impact on various cellular processes.Key words: RNA regulation, XRN2, XTBD, ribosome biogenesis, subcellular localization.
- Published
- 2021
8. Clinical significance of spatiotemporal transcriptional bursting and control
- Author
-
Xiangdong Wang and Diane Catherine Wang
- Subjects
Transcriptional Activation ,Medicine (General) ,Transcription, Genetic ,superenhancer ,Cell ,Medicine (miscellaneous) ,Biology ,medicine.disease_cause ,R5-920 ,Spatio-Temporal Analysis ,Transcriptional regulation ,medicine ,Humans ,spatiotemporal ,Transcriptional bursting ,Mechanism (biology) ,Cell growth ,Phenotype ,medicine.anatomical_structure ,Editorial ,RNA regulation ,transcriptional bursting ,Molecular Medicine ,Carcinogenesis ,Neuroscience ,Function (biology) ,transcriptional control - Abstract
The rapid development of technologies provides the potential to perform real‐time visualization of transcriptional bursting patterns, superenhancer formation and sensitivity to perturbation, and interactions between enhancers, promoters, and regulators during the burst. The transcriptional bursting‐induced fluctuation can modify cell capacities, cell–cell communications, cell responses to microenvironmental changes, and forms of cell death. A large number of clinical and translational studies describe the existence of heterogeneity among cells, tissues, and organs but mechanism‐based understanding of how and why the heterogeneity exists and how it is formed. The transcriptional bursting, fluctuation, and control determine the development of heterogeneity and optimize cell functions in the cell development and differentiation, contribute to the initiation of cell dysfunction and tumorigenesis in response to environments, and development/evolvement of hyper/hyposensitivity to drugs. Spatiotemporal monitoring of transcriptional bursting and control provides a new insight and deeper understanding of spatiotemporal molecular medicine by integrating the transcriptional positioning and function with cell phenotypes, cell–cell communication, and clinical phenomes.
- Published
- 2021
9. Phase-separated stress granules and processing bodies are compromised in Myotonic Dystrophy Type 1
- Author
-
Papavasiliou Pp, Judith E. Sleeman, Magon Ms, Alan R. Prescott, Gulyurtlu S, and Guest P
- Subjects
congenital, hereditary, and neonatal diseases and abnormalities ,Stress granule ,Chemistry ,medicine ,RNA ,Trinucleotide repeat disorder ,medicine.disease ,Protein kinase A ,Myotonic dystrophy ,Gene ,Cell biology ,Rna regulation ,Cytoplasmic Structure - Abstract
SummaryRNA regulation in mammalian cells requires complex physical compartmentalisation using structures thought to be formed by liquid-liquid phase separation. Disruption of these structures is implicated in numerous degenerative diseases. Myotonic Dystrophy Type 1 (DM1) is a multi-systemic trinucleotide repeat disorder resulting from a CTG expansion in the dystonia myotonica protein kinase gene (DMPK). The cellular hall-mark of DM1 is the formation of nuclear foci containing expanded DMPK RNA (CUGexp). We report here the deregulation of stress granules and processing bodies (P-bodies), two cytoplasmic structures key for mRNA regulation, in cell culture models of DM1. Alterations to the rates of formation and dispersal of stress granules suggest an altered ability to respond to stress associated with DM1, while changes to the structure and dynamics of stress granules and P-bodies suggest that a more widespread alteration to the biophysical properties of cellular structures may be a consequence of the presence of CUGexp RNA.
- Published
- 2021
10. The P1 and P2 helices of the Guanidinium-II riboswitch interact in a ligand-dependent manner
- Author
-
Martin Hengesbach, Fuks C, Nadine Schwierz, and Sebastian Falkner
- Subjects
Riboswitch ,Förster resonance energy transfer ,Dependent manner ,Chemistry ,Gene expression ,Biophysics ,Molecule ,Ligand (biochemistry) ,Small molecule ,Rna regulation - Abstract
Riboswitch RNAs regulate gene expression by conformational changes induced by environmental conditions and specific ligand binding. The guanidine-II riboswitch is proposed to bind the small molecule guanidinium and to subsequently form a kissing loop interaction between the P1 and P2 hairpins. While an interaction was shown for isolated hairpins in crystallization and EPR experiments, an intrastrand kissing loop formation has not been demonstrated. Here, we report the first evidence of this interaction in cis in a ligand and Mg2+ dependent manner. Using single-molecule FRET spectroscopy and detailed structural information from coarse-grained simulations, we observe and characterize three interconvertible states representing an open and kissing loop conformation as well as a novel Mg2+ dependent state for the guanidine-II riboswitch from E. coli. The results further substantiate the proposed switching mechanism and provide detailed insight into the regulation mechanism for the guanidine-II riboswitch class. Combining single molecule experiments and coarse-grained simulations therefore provides a promising perspective in resolving the conformational changes induced by environmental conditions and to yield molecular insights into RNA regulation.
- Published
- 2021
11. RNA and liquid-liquid phase separation
- Author
-
Qi Guo, Xiangmin Shi, and Xiangting Wang
- Subjects
0301 basic medicine ,Biological phenomenon ,Chemistry ,Biochemistry (medical) ,RNA ,QH426-470 ,Non-coding RNA ,Biochemistry ,Long non-coding RNA ,Article ,Liquid-liquid phase separation ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Order (biology) ,Transcriptional regulation ,030220 oncology & carcinogenesis ,RNA regulation ,Genetics ,Biophysics ,Liquid liquid ,Molecular Biology ,Function (biology) ,Long noncoding RNA - Abstract
Liquid-Liquid Phase Separation (LLPS) is a biological phenomenon that refers to the components of similar properties form droplets condensate in cells. These droplets play an important role in maintaining the stability of order in cells. In the studies of phase separation, weak multivalent interactions between proteins have always been the focus of attentions. With the deepening research of phase separation, more and more evidences show that RNA, especially long noncoding RNA (lncRNA), also plays an important regulatory role in the phase separation. We summarized recent researches between phase separation and RNA, and focused on the function of non-coding RNA (ncRNA) in the process of phase separation. In fact, phase separation and RNA have a two-way regulation relationship. Noncoding RNA usually recruits proteins as molecular scaffolds to drive phase separation. On the other hand, phase separation is also involved in RNA transcription, transport, metabolism and other processes.
- Published
- 2021
12. Analysis of Long Non-Coding RNA in Cryptosporidium parvum Reveals Significant Stage-Specific Antisense Transcription
- Author
-
Yiran Li, Rodrigo P. Baptista, Adam Sateriale, Boris Striepen, and Jessica C. Kissinger
- Subjects
0301 basic medicine ,Microbiology (medical) ,Immunology ,lcsh:QR1-502 ,Microbiology ,lcsh:Microbiology ,Transcriptome ,03 medical and health sciences ,lncRNA ,0302 clinical medicine ,parasitic diseases ,Gene expression ,parasite development ,Gene ,Host cell nucleus ,Genetics ,biology ,biology.organism_classification ,Long non-coding RNA ,Antisense RNA ,030104 developmental biology ,Infectious Diseases ,Cryptosporidium parvum ,Regulatory sequence ,RNA regulation ,Apicomplexa ,transcriptome ,030217 neurology & neurosurgery ,stranded RNA-Seq - Abstract
Cryptosporidium is a protist parasite that has been identified as the second leading cause of moderate to severe diarrhea in children younger than two and a significant cause of mortality worldwide. Cryptosporidium has a complex, obligate, intracellular but extra cytoplasmic lifecycle in a single host. How genes are regulated in this parasite remains largely unknown. Long non-coding RNAs (lncRNAs) play critical regulatory roles, including gene expression across a broad range of organisms. Cryptosporidium lncRNAs have been reported to enter the host cell nucleus and affect the host response. However, no systematic study of lncRNAs in Cryptosporidium has been conducted to identify additional lncRNAs. In this study, we analyzed a C. parvum in vitro strand-specific RNA-seq developmental time series covering both asexual and sexual stages to identify lncRNAs associated with parasite development. In total, we identified 396 novel lncRNAs, mostly antisense, with 86% being differentially expressed. Surprisingly, nearly 10% of annotated mRNAs have an antisense transcript. lncRNAs occur most often at the 3′ end of their corresponding sense mRNA. Putative lncRNA regulatory regions were identified and many appear to encode bidirectional promoters. A positive correlation between lncRNA and upstream mRNA expression was observed. Evolutionary conservation and expression of lncRNA candidates was observed between C. parvum, C. hominis and C. baileyi. Ten C. parvum protein-encoding genes with antisense transcripts have P. falciparum orthologs that also have antisense transcripts. Three C. parvum lncRNAs with exceptional properties (e.g., intron splicing) were experimentally validated using RT-PCR and RT-qPCR. This initial characterization of the C. parvum non-coding transcriptome facilitates further investigations into the roles of lncRNAs in parasite development and host-pathogen interactions.
- Published
- 2021
13. Novel insights into the m
- Author
-
Yiqing, Cai, Rui, Feng, Tiange, Lu, Xiaomin, Chen, Xiangxiang, Zhou, and Xin, Wang
- Subjects
N6-methyladenosine ,RNA regulation ,Tumorigenesis ,METTL3 ,Review - Abstract
N6-methyladenosine (m6A) is a prevalent internal RNA modification in higher eukaryotic cells. As the pivotal m6A regulator, RNA methyltransferase-like 3 (METTL3) is responsible for methyl group transfer in the progression of m6A modification. This epigenetic regulation contributes to the structure and functional regulation of RNA and further promotes tumorigenesis and tumor progression. Accumulating evidence has illustrated the pivotal roles of METTL3 in a variety of human cancers. Here, we systemically summarize the interaction between METTL3 and RNAs, and illustrate the multiple functions of METTL3 in human cancer. METLL3 is aberrantly expressed in a variety of tumors. Elevation of METTL3 is usually associated with rapid progression and poor prognosis of tumors. On the other hand, METTL3 may also function as a tumor suppressor in several cancers. Based on the tumor-promoting effect of METTL3, the possibility of applying METTL3 inhibitors is further discussed, which is expected to provide novel insights into antitumor therapy.
- Published
- 2020
14. lncRNAs in T lymphocytes: RNA regulation at the heart of the immune response
- Author
-
Leah M. Plasek and Saba Valadkhan
- Subjects
0301 basic medicine ,Physiology ,T-Lymphocytes ,Immunity ,Cell Differentiation ,Cell Biology ,Biology ,Rna regulation ,Cell biology ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Immune system ,Gene Expression Regulation ,030220 oncology & carcinogenesis ,T cell differentiation ,Cytotoxic T cell ,Animals ,Humans ,RNA, Long Noncoding ,Theme - Abstract
Genome-wide analyses in the last decade have uncovered the presence of a large number of long non-protein-coding transcripts that show highly tissue- and state-specific expression patterns. High-throughput sequencing analyses in diverse subsets of immune cells have revealed a complex and dynamic expression pattern for these long noncoding RNAs (lncRNAs) that correlate with the functional states of immune cells. Although the vast majority of lncRNAs expressed in immune cells remain unstudied, functional studies performed on a small subset have indicated that their state-specific expressions pattern frequently has a regulatory impact on the function of immune cells. In vivo and in vitro studies have pointed to the involvement of lncRNAs in a wide variety of cellular processes, including both the innate and adaptive immune response through mechanisms ranging from epigenetic and transcriptional regulation to sequestration of functional molecules in subcellular compartments. This review will focus mainly on the role of lncRNAs in CD4+ and CD8+ T cells, which play pivotal roles in adaptive immunity. Recent studies have pointed to key physiological functions for lncRNAs during several developmental and functional stages of the life cycle of lymphocytes. Although lncRNAs play important physiological roles in lymphocytic response to antigenic stimulation, differentiation into effector cells, and secretion of cytokines, their dysregulated expression can promote or sustain pathological states such as autoimmunity, chronic inflammation, cancer, and viremia. This, together with their highly cell type-specific expression patterns, makes lncRNAs ideal therapeutic targets and underscores the need for additional studies into the role of these understudied transcripts in adaptive immune response.
- Published
- 2020
15. Analysis of Long Non-Coding RNA in
- Author
-
Yiran, Li, Rodrigo P, Baptista, Adam, Sateriale, Boris, Striepen, and Jessica C, Kissinger
- Subjects
Cryptosporidium parvum ,Cryptosporidiosis ,Cryptosporidium ,Cellular and Infection Microbiology ,lncRNA ,parasitic diseases ,RNA regulation ,Humans ,RNA, Long Noncoding ,RNA, Messenger ,parasite development ,Child ,Apicomplexa ,transcriptome ,Original Research ,stranded RNA-Seq - Abstract
Cryptosporidium is a protist parasite that has been identified as the second leading cause of moderate to severe diarrhea in children younger than two and a significant cause of mortality worldwide. Cryptosporidium has a complex, obligate, intracellular but extra cytoplasmic lifecycle in a single host. How genes are regulated in this parasite remains largely unknown. Long non-coding RNAs (lncRNAs) play critical regulatory roles, including gene expression across a broad range of organisms. Cryptosporidium lncRNAs have been reported to enter the host cell nucleus and affect the host response. However, no systematic study of lncRNAs in Cryptosporidium has been conducted to identify additional lncRNAs. In this study, we analyzed a C. parvum in vitro strand-specific RNA-seq developmental time series covering both asexual and sexual stages to identify lncRNAs associated with parasite development. In total, we identified 396 novel lncRNAs, mostly antisense, with 86% being differentially expressed. Surprisingly, nearly 10% of annotated mRNAs have an antisense transcript. lncRNAs occur most often at the 3′ end of their corresponding sense mRNA. Putative lncRNA regulatory regions were identified and many appear to encode bidirectional promoters. A positive correlation between lncRNA and upstream mRNA expression was observed. Evolutionary conservation and expression of lncRNA candidates was observed between C. parvum, C. hominis and C. baileyi. Ten C. parvum protein-encoding genes with antisense transcripts have P. falciparum orthologs that also have antisense transcripts. Three C. parvum lncRNAs with exceptional properties (e.g., intron splicing) were experimentally validated using RT-PCR and RT-qPCR. This initial characterization of the C. parvum non-coding transcriptome facilitates further investigations into the roles of lncRNAs in parasite development and host-pathogen interactions.
- Published
- 2020
16. Records of RNA locations in living yeast revealed through covalent marks
- Author
-
Christopher P. Lapointe, Hugo C. Medina-Muñoz, Douglas F. Porter, and Marvin Wickens
- Subjects
Messenger RNA ,Multidisciplinary ,Saccharomyces cerevisiae Proteins ,RNA localization ,Endoplasmic reticulum ,RNA ,RNA, Fungal ,RNA surveillance ,Saccharomyces cerevisiae ,Biology ,Mitochondrion ,Biological Sciences ,Endoplasmic Reticulum ,Biochemistry ,Yeast ,Cell biology ,Mitochondria ,Organelle ,RNA regulation ,Humans ,RNA, Messenger ,Ribosomes ,Uridine ,localized RNA records - Abstract
Significance RNAs move within cells and often reside at specific locations. The need to detect those movements and locales across the transcriptome is pressing. We report an approach in living cells that provides a record of localization across the entire collection of RNAs a cell contains. It relies on covalently marking the RNA when it directly encounters a specific site. Using this approach, we identify a conserved battery of RNAs that are identified at more than one location in yeast and human cells, noncanonical modes of localization, and RNAs undergoing processing or surveillance at discrete subcellular locations. Our findings provide an entrée to the histories of individual RNA molecules through covalent marks., RNA movements and localization pervade biology, from embryonic development to disease. To identify RNAs at specific locations, we developed a strategy in which a uridine-adding enzyme is anchored to subcellular sites, where it directly marks RNAs with 3′ terminal uridines. This localized RNA recording approach yields a record of RNA locations, and is validated through identification of RNAs localized selectively to the endoplasmic reticulum (ER) or mitochondria. We identify a broad dual localization pattern conserved from yeast to human cells, in which the same battery of mRNAs encounter both ER and mitochondria in both species, and include an mRNA encoding a key stress sensor. Subunits of many multiprotein complexes localize to both the ER and mitochondria, suggesting coordinated assembly. Noncoding RNAs in the course of RNA surveillance and processing encounter both organelles. By providing a record of RNA locations over time, the approach complements those that capture snapshots of instantaneous positions.
- Published
- 2020
17. TRIM71 binds to IMP1 and is capable of positive and negative regulation of target RNAs
- Author
-
Daniel J. Foster, Hao-Ming Chang, Jeffrey R. Haswell, Richard I. Gregory, and Frank J. Slack
- Subjects
0301 basic medicine ,Carcinoma, Hepatocellular ,Deletion mutant ,RNA Stability ,Ubiquitin-Protein Ligases ,Biology ,Rna regulation ,Tripartite Motif Proteins ,03 medical and health sciences ,0302 clinical medicine ,Humans ,Point Mutation ,Protein Interaction Domains and Motifs ,RNA, Neoplasm ,Molecular Biology ,Cellular Senescence ,Cell Proliferation ,Sequence Deletion ,Point mutation ,Liver Neoplasms ,RNA ,RNA-Binding Proteins ,Cell Biology ,Hep G2 Cells ,Cell biology ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,030220 oncology & carcinogenesis ,biology.protein ,Mdm2 ,Developmental Biology ,Protein Binding ,Research Article - Abstract
TRIM71 is an important RNA-binding protein in development and disease, yet its direct targets have not been investigated globally. Here we describe a number of disease and developmentally-relevant TRIM71 RNA targets such as the MBNL family, LIN28B, MDM2, and TCF7L2. We describe a new role for TRIM71 as capable of positive or negative RNA regulation depending on the RNA target. We found that TRIM71 co-precipitated with IMP1 which could explain its multiple mechanisms of RNA regulation, as IMP1 is typically thought to stabilize RNAs. Deletion of the NHL domain of TRIM71 impacted its ability to bind to RNA and RNAs bound by congenital hydrocephalus-associated point mutations in the RNA-binding NHL domain of TRIM71 clustered closely with RNAs bound by the NHL deletion mutant. Our work expands the possible mechanisms by which TRIM71 may regulate RNAs and elucidates further potential RNA targets.
- Published
- 2020
18. Editorial: RNA Regulation in Development and Disease
- Author
-
Maritza Jaramillo, Chiara Gamberi, and Pascal Chartrand
- Subjects
disease ,RNA ,translational control ,RNA-binding protein ,RNA-binding proteins ,Disease ,Biology ,Rna regulation ,Cell biology ,Editorial ,Genetics ,mRNA localization ,development - Published
- 2020
19. Stepwise sRNA Targeting of Structured Bacterial mRNAsLeads to Abortive Annealing
- Author
-
Sarah A. Woodson and Ewelina M. Małecka
- Subjects
Messenger RNA ,Förster resonance energy transfer ,Chemistry ,Base pair ,RNA chaperone ,Transfer RNA ,Computational biology ,Single-molecule experiment ,Protein secondary structure ,Rna regulation - Abstract
Bacterial small RNAs (sRNAs) regulate the expression of hundreds of transcripts via base pairing mediated by the Hfq chaperone protein. sRNAs and the mRNA sites they target are heterogeneous in sequence, length, and secondary structure. To understand how Hfq can flexibly match diverse sRNA and mRNA pairs, we developed a single-molecule Forster resonance energy transfer (smFRET) platform that visualizes the target search on time scales relevant in cells. Here we show that unfolding of target secondary structure on Hfq creates a kinetic energy barrier that determines whether target recognition succeeds or aborts before a stable anti-sense complex is achieved. Premature dissociation of the sRNA can be alleviated by strong RNA-Hfq interactions, explaining why sRNAs have different target recognition profiles. We propose that the diverse sequences and structures of Hfq substrates creates an additional layer of information that tunes the efficiency and selectivity of non-coding RNA regulation in bacteria.
- Published
- 2020
20. Epigenetic Signalling and RNA Regulation in Cardiovascular Diseases
- Author
-
Fabio Martelli, Tiziana Bacchetti, Sandra Atlante, Carlo Gaetano, Antonella Farsetti, and Alessia Mongelli
- Subjects
chemistry.chemical_compound ,Chronic disease ,Signalling ,chemistry ,Nucleic acid ,RNA ,biology_other ,Epigenetics ,Biology ,DNA ,Rna regulation ,Cell biology - Abstract
RNA epigenetics is perhaps the most recent aspect of interest for translational epigeneticists. RNA modifications create such an extensive network of epigenetically driven combination whose role in physiology and pathophysiology is still far from being elucidated. Not surprisingly, some of the players determining changes into RNA structure are in common with those involved in DNA and chromatin structure regulation, while other molecules seem very specific to RNA. It is envisaged, then, that new small molecules, acting selectively on RNA epigenetic changes, will be reported soon, opening new therapeutic interventions based on the correction of the RNA epigenetic landscape. In this review, we shall summarize some aspects of RNA epigenetics limited to those in which the potential clinical translatability to cardiovascular disease is emerging.
- Published
- 2019
21. RNA Binding and HEPN-Nuclease Activation Are Decoupled in CRISPR-Cas13a
- Author
-
Gavin J. Knott, Jennifer A. Doudna, Mitchell R. O’Connell, Akshay Tambe, and Alexandra East-Seletsky
- Subjects
0301 basic medicine ,CRISPR-Cas systems ,Cas13a ,Base pair ,RNA biology ,Medical Physiology ,CRISPR-Associated Proteins ,Computational biology ,Cleavage (embryo) ,Article ,General Biochemistry, Genetics and Molecular Biology ,Rna regulation ,RNA specificity ,03 medical and health sciences ,Genetics ,Humans ,CRISPR ,Nucleotide ,chemistry.chemical_classification ,Nuclease ,Cas13 ,biology ,RNA ,Endonucleases ,030104 developmental biology ,Enzyme ,chemistry ,C2c2 ,biology.protein ,Biochemistry and Cell Biology ,CRISPR-Cas Systems ,Carrier Proteins ,Guide ,RNA, Guide, Kinetoplastida - Abstract
CRISPR-Cas13a enzymes are RNA-guided, RNA-activated ribonucleases. Their properties have been exploited as powerful tools for RNA detection, RNA imaging and RNA regulation. However, the relationship between target RNA binding and HEPN (higher-eukaryotes-and-prokaryotes nucleotide-binding)- domain nuclease activation is not well understood. Using sequencing experiments coupled with in vitro biochemistry, we find that Cas13a’s target RNA binding affinity and HEPN-nuclease activity are differentially affected by the number of and position of mismatches between the guide and target. We identify a central ‘binding seed’ where perfect base pairing is absolutely required for target binding, and a separate ‘nuclease switch’ where imperfect base-pairing results in tight binding but no HEPN-nuclease activation. These results demonstrate that the binding and cleavage activities of Cas13a are decoupled, highlighting a complex specificity landscape. Our findings underscore a need to consider the range of effects off-target recognition has on Cas13a’s RNA binding and cleavage behavior for RNA-targeting tool development.
- Published
- 2018
22. Antisense probing of dynamic RNA structures
- Author
-
Lydia M. Contreras and Alexandra J. Lukasiewicz
- Subjects
Transcription, Genetic ,Molecular Probe Techniques ,Computational biology ,General Biochemistry, Genetics and Molecular Biology ,Rna regulation ,03 medical and health sciences ,RNA, Antisense ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,biology ,Chemistry ,030302 biochemistry & molecular biology ,Tetrahymena ,Ribozyme ,Intron ,RNA ,biology.organism_classification ,Small molecule ,Footprinting ,Introns ,High-Throughput Screening Assays ,Molecular Probes ,Protein Biosynthesis ,biology.protein ,Nucleic Acid Conformation ,RNA, Viral ,RNA, Protozoan ,Plasmids - Abstract
RNA regulation is influenced by the dynamic changes in conformational accessibility on the transcript. Here we discuss the initial validation of a cell-free antisense probing method for structured RNAs, using the Tetrahymena group I intron as a control target. We observe changes in signal that qualitatively match prior traditional DMS footprinting experiments. Importantly, we have shown that application of this technique can elucidate new RNA information given its sensitivity for detecting rare intermediates that are not as readily observed by single-hit kinetics chemical probing techniques. Observing changes in RNA accessibility has broad applications in determining the effect that regulatory elements have on regional structures. We speculate that this method could be useful in quickly observing those interactions, along with other phenomena that influence RNA accessibility including RNA-RNA interactions and small molecules.
- Published
- 2019
23. RNA Regulations and Functions Decoded by Transcriptome-wide RNA Structure Probing
- Author
-
Qiangfeng Cliff Zhang, Lei Sun, and Meiling Piao
- Subjects
0301 basic medicine ,Transcription, Genetic ,RNA Splicing ,Systems biology ,Review ,Computational biology ,Biology ,Bioinformatics ,Biochemistry ,Structure–function relationship ,Rna regulation ,Nucleic acid secondary structure ,Transcriptome ,03 medical and health sciences ,Genetics ,Animals ,Humans ,Nucleic acid structure ,RNA structurome ,lcsh:QH301-705.5 ,Molecular Biology ,RNA ,RNA secondary structure ,Computational Mathematics ,030104 developmental biology ,lcsh:Biology (General) ,Protein Biosynthesis ,RNA regulation ,Nucleic Acid Conformation ,RNA structure probing - Abstract
RNA folds into intricate structures that are crucial for its functions and regulations. To date, a multitude of approaches for probing structures of the whole transcriptome, i.e., RNA structuromes, have been developed. Applications of these approaches to different cell lines and tissues have generated a rich resource for the study of RNA structureâfunction relationships at a systems biology level. In this review, we first introduce the designs of these methods and their applications to study different RNA structuromes. We emphasize their technological differences especially their unique advantages and caveats. We then summarize the structural insights in RNA functions and regulations obtained from the studies of RNA structuromes. And finally, we propose potential directions for future improvements and studies. Keywords: RNA structure probing, RNA structurome, RNA secondary structure, Structureâfunction relationship, RNA regulation
- Published
- 2017
24. Stepwise sRNA targeting of structured bacterial mRNAs leads to abortive annealing
- Author
-
Sarah A. Woodson and Ewelina M. Małecka
- Subjects
Base pair ,RNA Stability ,Computational biology ,Host Factor 1 Protein ,Biology ,Protein Structure, Secondary ,Article ,Nucleic acid secondary structure ,Rna regulation ,Structure-Activity Relationship ,03 medical and health sciences ,0302 clinical medicine ,Fluorescence Resonance Energy Transfer ,RNA, Messenger ,Molecular Biology ,Protein secondary structure ,Protein Unfolding ,030304 developmental biology ,0303 health sciences ,Messenger RNA ,Escherichia coli K12 ,Protein Stability ,Escherichia coli Proteins ,Gene Expression Regulation, Bacterial ,Cell Biology ,Single-molecule FRET ,Kinetics ,RNA, Bacterial ,Förster resonance energy transfer ,Microscopy, Fluorescence ,Transfer RNA ,Nucleic Acid Conformation ,RNA, Small Untranslated ,Single-Cell Analysis ,030217 neurology & neurosurgery - Abstract
Bacterial small RNAs (sRNAs) regulate the expression of hundreds of transcripts via base pairing mediated by the Hfq chaperone protein. sRNAs and the mRNA sites they target are heterogeneous in sequence, length, and secondary structure. To understand how Hfq can flexibly match diverse sRNA and mRNA pairs, we developed a single-molecule Förster resonance energy transfer (smFRET) platform that visualizes the target search on time scales relevant in cells. Here we show that unfolding of target secondary structure on Hfq creates a kinetic energy barrier that determines whether target recognition succeeds or aborts before a stable anti-sense complex is achieved. Premature dissociation of the sRNA can be alleviated by strong RNA-Hfq interactions, explaining why sRNAs have different target recognition profiles. We propose that the diverse sequences and structures of Hfq substrates creates an additional layer of information that tunes the efficiency and selectivity of non-coding RNA regulation in bacteria.
- Published
- 2021
25. RNA-Seq unveils new attributes of the heterogeneous Salmonella-host cell communication
- Author
-
M. Graciela Pucciarelli and Francisco García-del Portillo
- Subjects
0301 basic medicine ,Salmonella ,RNA-Seq ,Computational biology ,medicine.disease_cause ,Microbiology ,Rna regulation ,03 medical and health sciences ,medicine ,Animals ,Humans ,Point of View ,Molecular Biology ,biology ,Sequence Analysis, RNA ,Macrophages ,High-Throughput Nucleotide Sequencing ,Salmonella enterica ,RNA ,Epithelial Cells ,Gene Expression Regulation, Bacterial ,Cell Biology ,biology.organism_classification ,RNA, Bacterial ,030104 developmental biology ,Host-Pathogen Interactions ,Bacteria - Abstract
High-throughput RNA sequencing (RNA-Seq) has uncovered hundreds of small RNAs and complex modes of RNA regulation in every bacterium analyzed to date. This complexity agrees with the adaptability of most bacteria to varied environments including, in the case of pathogens, the new niches encountered in the host. Recent RNA-Seq studies have analyzed simultaneously gene expression in the intracellular pathogen Salmonella enterica and infected host cells at population and single-cell level. Distinct polarization states or interferon responses in the infected macrophage were linked to variable growth rates or activities of defined virulence regulators in intra-phagosomal bacteria. Intracellular Salmonella, however, exhibit disparate intracellular lifestyles depending the host cell, ranging from a hyper-replicative cytosolic state in epithelial cells to a non-replicative intra-phagosomal condition in varied host cell types. The basis of such diverse pathogen-host communications could be examined by RNA-Seq studies in single intracellular Salmonella cells, certainly a challenge for future investigations.
- Published
- 2017
26. Advances that facilitate the study of large RNA structure and dynamics by nuclear magnetic resonance spectroscopy
- Author
-
Sarah C. Keane and Huaqun Zhang
- Subjects
cryo‐electron microscopy ,Riboswitch ,Central dogma of molecular biology ,Computational biology ,X‐ray crystallography ,Biology ,Biochemistry ,03 medical and health sciences ,RNA interference ,Gene expression ,RNA Structure, Dynamics, and Chemistry ,Nucleic acid structure ,RNA structure ,Nuclear Magnetic Resonance, Biomolecular ,Molecular Biology ,nuclear magnetic resonance spectroscopy ,030304 developmental biology ,0303 health sciences ,030302 biochemistry & molecular biology ,RNA ,Influence of RNA Structure in Biological Systems ,Non-coding RNA ,Primer ,Protein tertiary structure ,Regulatory RNAs ,RNA regulation ,chemical probing ,Nucleic Acid Conformation - Abstract
The characterization of functional yet nonprotein coding (nc) RNAs has expanded the role of RNA in the cell from a passive player in the central dogma of molecular biology to an active regulator of gene expression. The misregulation of ncRNA function has been linked with a variety of diseases and disorders ranging from cancers to neurodegeneration. However, a detailed molecular understanding of how ncRNAs function has been limited; due, in part, to the difficulties associated with obtaining high‐resolution structures of large RNAs. Tertiary structure determination of RNA as a whole is hampered by various technical challenges, all of which are exacerbated as the size of the RNA increases. Namely, RNAs tend to be highly flexible and dynamic molecules, which are difficult to crystallize. Biomolecular nuclear magnetic resonance (NMR) spectroscopy offers a viable alternative to determining the structure of large RNA molecules that do not readily crystallize, but is itself hindered by some technical limitations. Recently, a series of advancements have allowed the biomolecular NMR field to overcome, at least in part, some of these limitations. These advances include improvements in sample preparation strategies as well as methodological improvements. Together, these innovations pave the way for the study of ever larger RNA molecules that have important biological function. This article is categorized under: RNA Structure and Dynamics > RNA Structure, Dynamics, and ChemistryRegulatory RNAs/RNAi/Riboswitches > Regulatory RNAsRNA Structure and Dynamics > Influence of RNA Structure in Biological Systems, Overview of important sample preparation and methodological advancements that facilitate the study of large RNA structure and dynamics by nuclear magnetic resonance spectroscopy. These innovations pave the way for the study of previously intractable systems.
- Published
- 2019
27. Biochemical and Next Generation Sequencing Approaches to Study RNA Regulation
- Author
-
Aaron C. Goldstrohm and Eric J. Wagner
- Subjects
RNA metabolism ,RNA Stability ,Rna processing ,Sequence analysis ,Sequence Analysis, RNA ,High-Throughput Nucleotide Sequencing ,RNA-Binding Proteins ,Plasma protein binding ,Computational biology ,Biology ,General Biochemistry, Genetics and Molecular Biology ,DNA sequencing ,Rna regulation ,Protein Biosynthesis ,Protein biosynthesis ,Humans ,RNA ,RNA Processing, Post-Transcriptional ,Molecular Biology ,Protein Binding - Published
- 2019
28. Keth-seq for transcriptome-wide RNA structure mapping
- Author
-
Yushu Yuan, Lulu Hu, Shixi Yang, Fang Wang, Tong Wu, Jing Gong, Xiaocheng Weng, Kai Chen, Honghui Ma, Yi Chen, Chuan He, Qiangfeng Cliff Zhang, Pingluan Wang, Guan-Zheng Luo, and Xiang Zhou
- Subjects
RNA Folding ,Guanine ,Computational biology ,Article ,Rna regulation ,Nucleic acid secondary structure ,Transcriptome ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,Animals ,Humans ,Nucleic acid structure ,Molecular Biology ,Embryonic Stem Cells ,030304 developmental biology ,0303 health sciences ,Aldehydes ,030302 biochemistry & molecular biology ,Nucleic Acid Heteroduplexes ,High-Throughput Nucleotide Sequencing ,Cell Biology ,Butanones ,chemistry ,Rna labeling ,Nucleic Acid Conformation ,RNA ,Function (biology) ,HeLa Cells - Abstract
RNA secondary structure is critical to RNA regulation and function. We report a new N3-kethoxal reagent that allows fast and reversible labeling of single-stranded guanine bases in live cells. This N3-kethoxal-based chemistry allows efficient RNA labeling under mild conditions and transcriptome-wide RNA secondary structure mapping.
- Published
- 2019
29. A Heterocyst-Specific Antisense RNA Contributes to Metabolic Reprogramming in Nostoc sp. PCC 7120
- Author
-
Agustín Vioque, Elvira Olmedo-Verd, Alicia M. Muro-Pastor, Manuel Brenes-Álvarez, Brenes-Álvarez, Manuel [0000-0002-6452-5557], Vioque, Agustín [0000-0002-3975-7348], Muro-Pastor, Alica M. [0000-0003-2503-6336], Brenes-Álvarez, Manuel, Vioque, Agustín, and Muro-Pastor, Alica M.
- Subjects
Ribonuclease III ,0301 basic medicine ,Nostoc ,Physiology ,RNase III ,030106 microbiology ,Plant Science ,03 medical and health sciences ,Transcription (biology) ,Gene expression ,Transcriptional regulation ,RNA, Antisense ,Heterocyst ,CO2 fixation ,Sedoheptulose-1,7- bisphosphatase ,biology ,Anabaena ,Gene Expression Regulation, Bacterial ,Cell Biology ,General Medicine ,Carbon Dioxide ,biology.organism_classification ,Phosphoric Monoester Hydrolases ,Fructose-Bisphosphatase ,Antisense RNA ,Cell biology ,030104 developmental biology ,Regulon ,Metabolic Engineering ,RNA regulation ,Fructose-1,6-bisphosphatase - Abstract
Upon nitrogen deficiency, some filamentous cyanobacteria differentiate specialized cells, called heterocysts, devoted to N2 fixation. Heterocysts appear regularly spaced along the filaments and exhibit structural and metabolic adaptations, such as loss of photosynthetic CO2 fixation or increased respiration, to provide a proper microaerobic environment for its specialized function. Heterocyst development is under transcriptional control of the global nitrogen regulator NtcA and the specific regulator HetR. Transcription of a large number of genes is induced or repressed upon nitrogen deficiency specifically in cells undergoing differentiation. In recent years, the HetR regulon has been described to include heterocyst-specific trans-acting small RNAs and antisense RNAs (asRNAs), suggesting that there is an additional layer of post-transcriptional regulation involved in heterocyst development. Here, we characterize in the cyanobacterium Nostoc (Anabaena) sp. PCC 7120 an asRNA, that we call as_glpX, transcribed within the glpX gene encoding the Calvin cycle bifunctional enzyme sedoheptulose-1,7- bisphosphatase/fructose-1,6-bisphosphatase (SBPase). Transcription of as_glpX is restricted to heterocysts and is induced very early during the process of differentiation. Expression of as_glpX RNA promotes the cleavage of the glpX mRNA by RNase III, resulting in a reduced amount of SBPase. Therefore, the early expression of this asRNA could contribute to the quick shut-down of CO2 fixation in those cells in the filament that are undergoing differentiation into heterocysts. In summary, as_glpX is the first naturally occurring asRNA shown to rapidly and dynamically regulate metabolic transformation in Nostoc heterocysts. The use of antisense transcripts to manipulate gene expression specifically in heterocysts could became a useful tool for metabolic engineering in cyanobacteria.
- Published
- 2019
30. Programmable RNA-Guided RNA Effector Proteins Built from Human Parts
- Author
-
Huiqing Zhou, Zijie Zhang, Simone Rauch, Bryan C. Dickinson, Michael Srienc, and Emily He
- Subjects
Genetic enhancement ,Computational biology ,Biology ,Protein Engineering ,Transfection ,General Biochemistry, Genetics and Molecular Biology ,Rna regulation ,03 medical and health sciences ,Synthetic biology ,0302 clinical medicine ,Transcription Activator-Like Effector Nucleases ,Escherichia coli ,Humans ,RNA, Small Interfering ,Rna targeting ,030304 developmental biology ,Gene Editing ,0303 health sciences ,Effector ,RNA ,A protein ,HEK293 Cells ,Gene Knockdown Techniques ,Protein Biosynthesis ,Proteolysis ,CRISPR-Cas Systems ,030217 neurology & neurosurgery ,RNA, Guide, Kinetoplastida - Abstract
Epitranscriptomic regulation controls information flow through the central dogma and provides unique opportunities for manipulating cells at the RNA level. However, both fundamental studies and potential translational applications are impeded by a lack of methods to target specific RNAs with effector proteins. Here, we present CRISPR-Cas-inspired RNA targeting system (CIRTS), a protein engineering strategy for constructing programmable RNA control elements. We show that CIRTS is a simple and generalizable approach to deliver a range of effector proteins, including nucleases, degradation machinery, translational activators, and base editors to target transcripts. We further demonstrate that CIRTS is not only smaller than naturally occurring CRISPR-Cas programmable RNA binding systems but can also be built entirely from human protein parts. CIRTS provides a platform to probe fundamental RNA regulatory processes, and the human-derived nature of CIRTS provides a potential strategy to avoid immune issues when applied to epitranscriptome-modulating therapies.
- Published
- 2018
31. Mapping of In Vivo RNA-Binding Sites by Ultraviolet (UV)-Cross-Linking Immunoprecipitation (CLIP)
- Author
-
Aldo Mele, Robert B. Darnell, Ka Ying Sharon Hung, and Jennifer C. Darnell
- Subjects
0301 basic medicine ,RNA metabolism ,Binding Sites ,Immunoprecipitation ,Chemistry ,Ultraviolet Rays ,RNA ,RNA-Binding Proteins ,General Biochemistry, Genetics and Molecular Biology ,Cell biology ,Rna regulation ,Normal cell ,03 medical and health sciences ,030104 developmental biology ,In vivo ,Binding site ,Function (biology) - Abstract
RNA “CLIP” (cross-linking immunoprecipitation), the method by which RNA–protein complexes are covalently cross-linked and purified and the RNA sequenced, has attracted attention as a powerful means of developing genome-wide maps of direct, functional RNA–protein interaction sites. These maps have been used to identify points of regulation, and they hold promise for understanding the dynamics of RNA regulation in normal cell function and its dysregulation in disease.
- Published
- 2018
32. GED: a manually curated comprehensive resource for epigenetic modification of gametogenesis
- Author
-
Wen Yang, Yang Wang, Jinlian Hua, Can Liu, Qinghua Jiang, Wenjing Wang, Weiyang Bai, and Mingzhi Liao
- Subjects
0301 basic medicine ,Databases, Factual ,biology ,Computer science ,Computational biology ,DNA Methylation ,Bioinformatics ,Gametogenesis ,Epigenesis, Genetic ,Rna regulation ,MicroRNAs ,03 medical and health sciences ,030104 developmental biology ,Histone ,Homo sapiens ,microRNA ,DNA methylation ,biology.protein ,Animals ,Humans ,Epigenetics ,Molecular Biology ,Gene ,Information Systems - Abstract
Reproductive infertility affects seventh of couples, which is most attributed to the obstacle of gametogenesis. Characterizing the epigenetic modification factors involved in gametogenesis is fundamental to understand the molecular mechanisms and to develop treatments for human infertility. Although the genetic factors have been implicated in gametogenesis, no dedicated bioinformatics resource for gametogenesis is available. To elucidate the relationship of epigenetic modification and mammalian gametogenesis, we developed a new database, gametogenesis epigenetic modification database (GED), a manually curated database, which aims at providing a comprehensive resource of epigenetic modification of gametogenesis. The database integrates three kinds information of epigenetic modifications during gametogenesis (DNA methylation, histone modification and RNA regulation), and the gametogenesis has been detailed as 16 stages in seven mammal species (Homo sapiens, Mus musculus, Rattus norvegicus, Sus scrofa, Bos taurus, Capra hircus and Ovis aries). Besides, we have predicted the linear pathways of epigenetic modification which were composed of 211 genes/proteins and microRNAs that were involved in gametogenesis. GED is a user-friendly Web site, through which users can obtain the comprehensive epigenetic factor information and molecular pathways by visiting our database freely. GED is free available at http://gametsepi.nwsuaflmz.com.
- Published
- 2016
33. Introduction: Dynamics of RNA Regulation in the Immune System Special Issue
- Author
-
Shizuo Akira and Kazuhiko Maeda
- Subjects
0301 basic medicine ,03 medical and health sciences ,030104 developmental biology ,Immune system ,Immunology ,Dynamics (mechanics) ,Immunology and Allergy ,General Medicine ,Computational biology ,Biology ,Rna regulation - Published
- 2017
34. Effective RNA Regulation by Combination of Multiple Programmable RNA-Binding Proteins
- Author
-
Shiroh Futaki, Misaki Sugimoto, Akiyo Suda, and Miki Imanishi
- Subjects
Untranslated region ,RNA-binding protein ,lcsh:Technology ,lcsh:Chemistry ,03 medical and health sciences ,Gene expression ,General Materials Science ,PUF ,lcsh:QH301-705.5 ,Instrumentation ,030304 developmental biology ,Fluid Flow and Transfer Processes ,0303 health sciences ,Expression vector ,lcsh:T ,Chemistry ,Process Chemistry and Technology ,030302 biochemistry & molecular biology ,General Engineering ,RNA ,Translation (biology) ,RNA binding protein ,lcsh:QC1-999 ,Computer Science Applications ,Cell biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,lcsh:TA1-2040 ,RNA regulation ,RNA splicing ,lcsh:Engineering (General). Civil engineering (General) ,lcsh:Physics ,Function (biology) - Abstract
RNAs play important roles in gene expression through translation and RNA splicing. Regulation of specific RNAs is useful to understand and manipulate specific transcripts. Pumilio and fem-3 mRNA-binding factor (PUF) proteins, programmable RNA-binding proteins, are promising tools for regulating specific RNAs by fusing them with various functional domains. The key question is: How can PUF-based molecular tools efficiently regulate RNA functions? Here, we show that the combination of multiple PUF proteins, compared to using a single PUF protein, targeting independent RNA sequences at the 3&prime, untranslated region (UTR) of a target transcript caused cooperative effects to regulate the function of the target RNA by luciferase reporter assays. It is worth noting that a higher efficacy was achieved with smaller amounts of each PUF expression vector introduced into the cells compared to using a single PUF protein. This strategy not only efficiently regulates target RNA functions but would also be effective in reducing off-target effects due to the low doses of each expression vector.
- Published
- 2020
35. Lessons from studying the AU-rich elements in chronic inflammation and autoimmunity
- Author
-
Niki Lourou, Dimitris L. Kontoyiannis, and Maxim Gavriilidis
- Subjects
0301 basic medicine ,Immunology ,Inflammation ,Computational biology ,Biology ,medicine.disease_cause ,Regulatory rna ,Autoimmune Diseases ,Autoimmunity ,Rna regulation ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Animals ,Humans ,Immunology and Allergy ,Functional studies ,AU Rich Elements ,030203 arthritis & rheumatology ,AU-rich element ,RNA-Binding Proteins ,Translation (biology) ,030104 developmental biology ,Gene Expression Regulation ,Chronic Disease ,medicine.symptom - Abstract
AU-rich elements (AREs) comprise one of the most widely studied families of regulatory RNA structures met in RNAs engaged in complex immunological reactions. A multitude of genetic, molecular, holistic and functional studies have been utilized for the analyses of the AREs and their interactions to proteins that bind to them. Data stemming from these studies brought forth a world of RNA-related check-points against infection, chronic inflammation, tumor associated immunity, and autoimmunity; and the interest to capitalize the interactions of AREs for clinical management and therapy. They also provided lessons on the cellular capabilities of post-transcriptional control. Originally thought as transcript-restricted regulators of turnover and translation, ARE-binding proteins do in fact harbor great versatility and interactivity across nuclear and cytoplasmic compartments; and act as functional coordinators of immune-cellular programs. Harnessing these deterministic functions requires extensive knowledge of their synergies or antagonisms at a cell-specific level; but holds great promise since it can provide the efficacy of combinatorial therapies with single agents.
- Published
- 2019
36. Long non-coding RNAs: crucial regulators of gastrointestinal cancer cell proliferation
- Author
-
Shuiping Liu, Xiaotong Hu, and Jiaxin Chen
- Subjects
0301 basic medicine ,Cancer Research ,Immunology ,Review Article ,Biology ,lcsh:RC254-282 ,Rna regulation ,law.invention ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,law ,medicine ,Gastrointestinal cancer ,lcsh:QH573-671 ,Gene ,lcsh:Cytology ,Cell growth ,Cell Biology ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Lncrna expression ,medicine.disease ,030104 developmental biology ,030220 oncology & carcinogenesis ,Potential biomarkers ,Cancer research ,Suppressor ,Signal transduction - Abstract
Studies of long non-coding RNAs (lncRNAs) have been prevalent in the field of non-coding RNA regulation in recent years. LncRNAs exert crucial effects on malignant cell processes in the gastrointestinal system, including proliferation. Aberrant lncRNA expression, through both oncogenes and tumor suppressor genes, is instrumental to tumor cell proliferation. Here, we summarize the different molecular mechanisms and relevant signaling pathways through which multifarious lncRNAs regulate cell proliferation and we show that lncRNAs are potential biomarkers for gastrointestinal cancers.
- Published
- 2018
37. A Stress Response that Monitors and Regulates mRNA Structure Is Central to Cold Shock Adaptation
- Author
-
David H. Burkhardt, Jonathan S. Weissman, Carol A. Gross, Silvi Rouskin, Yan Zhang, Gene-Wei Li, Massachusetts Institute of Technology. Department of Biology, and Whitehead Institute for Biomedical Research
- Subjects
0301 basic medicine ,RNA Stability ,Messenger ,translation ,Medical and Health Sciences ,cold shock proteins ,Protein biosynthesis ,Ribosome profiling ,Escherichia coli Proteins ,Bacterial ,Translation (biology) ,Biological Sciences ,mRNA surveillance ,Cold shock response ,Cell biology ,Cold Temperature ,RNA, Bacterial ,cold shock ,RNA regulation ,Physical Injury - Accidents and Adverse Effects ,1.1 Normal biological development and functioning ,Climate Change ,RNase R ,Biology ,Article ,03 medical and health sciences ,Structure-Activity Relationship ,Bacterial Proteins ,Underpinning research ,DMS-seq ,Genetics ,Escherichia coli ,RNA, Messenger ,Heat shock ,Molecular Biology ,ribosome profiling ,030102 biochemistry & molecular biology ,Cold-Shock Response ,Cell Biology ,Gene Expression Regulation, Bacterial ,RNA secondary structure ,Open reading frame ,030104 developmental biology ,Gene Expression Regulation ,Protein Biosynthesis ,Exoribonucleases ,Cold Shock Proteins and Peptides ,RNA ,Nucleic Acid Conformation ,Generic health relevance ,5' Untranslated Regions ,Developmental Biology - Abstract
Temperature influences the structural and functional properties of cellular components, necessitating stress responses to restore homeostasis following temperature shift. Whereas the circuitry controlling the heat shock response is well understood, that controlling the E. coli cold shock adaptation program is not. We found that during the growth arrest phase (acclimation) that follows shift to low temperature, protein synthesis increases, and open reading frame (ORF)-wide mRNA secondary structure decreases. To identify the regulatory system controlling this process, we screened for players required for increased translation. We identified a two-member mRNA surveillance system that enables recovery of translation during acclimation: RNase R assures appropriate mRNA degradation and the Csps dynamically adjust mRNA secondary structure to globally modulate protein expression level. An autoregulatory switch in which Csps tune their own expression to cellular demand enables dynamic control of global translation. The universality of Csps in bacteria suggests broad utilization of this control mechanism. Zhang et al. identified an mRNA structure surveillance system mediated by Csps and RNase R that facilitates translation recovery after cold shock in E. coli. Their work proves insights into a post-transcriptionally regulated bacterial stress response and suggests broad utilization of this control mechanism across all bacteria., Center for RNA Systems Biology (Grant P50 GM102706), National Institutes of Health (U.S.) (Grant K99GM105913)
- Published
- 2017
38. Computational Modeling of Protein-RNA Interactions
- Author
-
Yaron Orenstein
- Subjects
0301 basic medicine ,Structure (mathematical logic) ,business.industry ,Mechanism (biology) ,Experimental data ,RNA ,Biology ,Machine learning ,computer.software_genre ,Bioinformatics ,Field (computer science) ,Rna regulation ,03 medical and health sciences ,030104 developmental biology ,RNA Sequence ,Artificial intelligence ,Nucleic acid structure ,business ,computer - Abstract
Protein-RNA interactions, mediated through both RNA sequence and structure, play vital role in all cellular processes. In recent years, technologies have been developed to measure these interactions in high-throughput manner. Researchers would like to infer accurate models from the experimental data in order to predict new interactions and better understand the underlying binding mechanism. In this tutorial, I will present the main computational challenges in incorporating RNA structure information into computational algorithms and models. I will describe in detail two state-of-the-art methods to infer structure-based models from experimental data and discuss their strengths and weakness. I will conclude with open problems in the field.
- Published
- 2017
39. Serotonin 2C Receptor as a Superhero: Diversities and Talents in the RNA Universe for Editing, Variant, Small RNA and Other Expected Functional RNAs
- Author
-
Michihisa Tohda
- Subjects
Pharmacology ,Genetics ,Small RNA ,Mental Disorders ,lcsh:RM1-950 ,Genetic Variation ,RNA ,RNA-binding protein ,Serotonin 2C Receptor ,Computational biology ,Biology ,Rna regulation ,RNA silencing ,lcsh:Therapeutics. Pharmacology ,RNA editing ,RNA, Small Nuclear ,Receptor, Serotonin, 5-HT2C ,Animals ,Humans ,Molecular Medicine ,RNA Editing ,RNA, Messenger ,Receptor - Abstract
The serotonin 2C receptor subtype (5-HT2C) has a unique profession and continues to provide exciting and critical new information. The 5-HT2C is modulated at the RNA level by several mechanisms, including editing, short variant generation, and small RNAs. Recently, these phenomena, which had been demonstrated individually, were shown to be associated with each other. At present, many reports provide information about the influence of RNA regulation on receptor protein activities and expression, which was thought to be the final functional product. However, complicated behavior at the RNA stage allows us to imagine that the RNA itself has functional roles in the RNA universe. The 5-HT2C RNA may play several roles. This review will outline previous 5-HT2C studies and prospects for future studies. Keywords:: serotonin 2C receptor subtype (5-HT2C), RNA universe, RNA editing, small RNA, functional mental disease (FMD)
- Published
- 2014
40. The crossroads of RNA regulation and function in neurodevelopment
- Author
-
Mladen-Roko Rasin and Debra L. Silver
- Subjects
0301 basic medicine ,Gene Expression Regulation, Developmental ,Biology ,Nervous System ,Rna regulation ,Cell biology ,03 medical and health sciences ,030104 developmental biology ,Developmental Neuroscience ,Animals ,Humans ,RNA ,Function (biology) ,Developmental Biology - Published
- 2016
41. Determination of the Mechanism of RNA Regulation by CPSF30 Utilizing Both Biophysical and Structural Approaches
- Author
-
Jordan D. Pritts, Abdulafeez A. Oluyadi, Patrick L. Wintrode, Daniel Deredge, and Sarah L. J. Michel
- Subjects
Mechanism (biology) ,Chemistry ,Biophysics ,Rna regulation - Published
- 2019
42. The Influence of Competition Among C. elegans Small RNA Pathways on Development
- Author
-
Craig P. Hunter and Jimmy J. Zhuang
- Subjects
Small RNA ,lcsh:QH426-470 ,endogenous siRNAs ,Mutant ,Article ,03 medical and health sciences ,0302 clinical medicine ,RNA interference ,microRNA ,Genetics ,RasiRNA ,Genetics (clinical) ,Caenorhabditis elegans ,exogenous RNAi ,030304 developmental biology ,0303 health sciences ,biology ,enhanced RNAi ,fungi ,biology.organism_classification ,microRNAs ,Cell biology ,lcsh:Genetics ,RNA silencing ,RNA regulation ,Flux (metabolism) ,030217 neurology & neurosurgery - Abstract
Small RNAs play a variety of regulatory roles, including highly conserved developmental functions. Caenorhabditis elegans not only possesses most known small RNA pathways, it is also an easy system to study their roles and interactions during development. It has been proposed that in C. elegans, some small RNA pathways compete for access to common limiting resources. The strongest evidence supporting this model is that disrupting the production or stability of endogenous short interfering RNAs (endo-siRNAs) enhances sensitivity to experimentally induced exogenous RNA interference (exo-RNAi). Here, we examine the relationship between the endo-siRNA and microRNA (miRNA) pathways, and find that, consistent with competition among these endogenous small RNA pathways, endo-siRNA pathway mutants may enhance miRNA efficacy. Furthermore, we show that exo-RNAi may also compete with both endo-siRNAs and miRNAs. Our data thus provide support that all known Dicer-dependent small RNA pathways may compete for limiting common resources. Finally, we observed that both endo-siRNA mutants and animals experiencing exo-RNAi have increased expression of miRNA-regulated stage-specific developmental genes. These observations suggest that perturbing the small RNA flux and/or the induction of exo-RNAi, even in wild-type animals, may impact development via effects on the endo-RNAi and microRNA pathways.
- Published
- 2012
43. Author response: NOVA2-mediated RNA regulation is required for axonal pathfinding during development
- Author
-
John J. Fak, A. J. Hudspeth, Roberto Araya, Zhe Chen, Jeremy S. Duncan, Bernd Fritzsch, Yuhki Saito, Robert B. Darnell, Matteo Ruggiu, Ru Zhong, Christopher Y. Park, Brian A. Fabella, Soledad Miranda-Rottmann, and Harald J. Junge
- Subjects
Axonal Pathfinding ,Biology ,Neuroscience ,Rna regulation - Published
- 2016
44. The New Microbiology: A conference at the Institut de France
- Author
-
David Ribet, Hélène Bierne, Lilliana Radoshevich, Pascale Cossart, Interactions Bactéries-Cellules (UIBC), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Danone, La fondation L'Oreal, Institut Merieux, Inserm, Alfried Krupp von Bohlen und Halbach-Stiftung, and Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Subjects
MESH: Ecology ,[SDV]Life Sciences [q-bio] ,Institut de France ,General Biochemistry, Genetics and Molecular Biology ,MESH: RNA, Small Nuclear ,Microbiology ,Rna regulation ,German ,03 medical and health sciences ,"New Microbiology" Symposium ,Political science ,MESH: Microbiology ,030304 developmental biology ,0303 health sciences ,MESH: Humans ,General Immunology and Microbiology ,MESH: Genomics ,MESH: Proteomics ,030302 biochemistry & molecular biology ,The Renaissance ,General Medicine ,MESH: Metagenome ,language.human_language ,MESH: France ,MESH: Bacteria ,MESH: Bacterial Physiological Phenomena ,language ,General Agricultural and Biological Sciences - Abstract
International audience; In May 2012, three European Academies held a conference on the present and future of microbiology. The conference, entitled "The New Microbiology", was a joint effort of the French Academie des sciences, of the German National Academy of Sciences Leopoldina and of the British Royal Society. The organizers - Pascale Cossart and Philippe Sansonetti from the "Academie des sciences", David Holden and Richard Moxon from the "Royal Society", and Jorg Hacker and Jurgen Hesseman from the "Leopoldina Nationale Akademie der Wissenschaften" - wanted to highlight the current renaissance in the field of microbiology mostly due to the advent of technological developments and allowing for single-cell analysis, rapid and inexpensive genome-wide comparisons, sophisticated microscopy and quantitative large-scale studies of RNA regulation and proteomics. The conference took place in the historical Palais de l'Institut de France in Paris with the strong support of Jean-Francois Bach, Secretaire Perpetuel of the Academie des sciences.
- Published
- 2012
45. Differential Expressions of Nuclear Proteomes between Honeybee (Apis mellifera L.) Queen and Worker Larvae: A Deep Insight into Caste Pathway Decisions
- Author
-
Jianke Li, Fang Yu, Desalegn Begna, Feng Mao, and Bin Han
- Subjects
animal structures ,Proteome ,Zoology ,Real-Time Polymerase Chain Reaction ,Biochemistry ,Rna regulation ,Polyphenism ,Animals ,Electrophoresis, Gel, Two-Dimensional ,Protein Interaction Maps ,Nuclear protein ,Cell Nucleus ,Larva ,biology ,Ecology ,fungi ,Caste ,Gene Expression Regulation, Developmental ,Nuclear Proteins ,Reproducibility of Results ,General Chemistry ,Bees ,biology.organism_classification ,Insect Proteins ,Queen (butterfly) ,Instar ,Female - Abstract
Honeybees (Apis mellifera L.) possess individuals (castes) in their colonies, to which specific tasks are allocated. Owing to a difference in nutrition, the young female larvae develop into either a fertile queen or a sterile worker. Despite a series of investigations on the underlying mechanisms of honeybee caste polyphenism, information on proteins and enzymes involved in DNA and RNA regulation in the nucleus is still missing. The techniques of nuclear protein enrichment, two-dimensional electrophoresis, mass spectrometry and bioinformatics were applied to understand the nuclear proteome changes in response to changes in environmental settings (nutrition and time) during the early developmental stages at the third (72 h), fourth (96 h), and fifth (120 h) instars of the two caste intended larvae. A total of 120 differentially expressed nuclear proteins were identified in both caste intended larvae during these developmental stages. The third, fourth and fifth instars of queen prospective larvae expressed 69%, 84%, and 68% of the proteins that had altered expression, respectively. Particularly, the prospective queen larvae up-regulated most of the proteins with nuclear functions. In general, this changing nuclear proteome of the two caste intended larvae over the three developmental stages suggests variations in DNA and RNA regulating proteins and enzymes. These variations of proteins and enzymes involved in DNA and RNA regulation in response to differential nutrition between the two caste intended larvae lead the two caste larvae to pursue different developmental trajectories. Hence, this first data set of the nuclear proteome helps us to explore the innermost biological makings of queen and worker bee castes as early as before the 72 h (3rd instar). Also, it provides new insights into the honeybee's polymorphism at nuclear proteome level and paves new ways to understand mechanisms of caste decision in other eusocial insects.
- Published
- 2012
46. Pseudogenes are not pseudo any more
- Author
-
Yan-Zi Wen, Ling-Ling Zheng, Zhao-Rong Lun, Francisco J. Ayala, and Liang-Hu Qu
- Subjects
Genetics ,Cognitive science ,Transcription, Genetic ,Pseudogene ,Trypanosoma brucei brucei ,PTEN Phosphohydrolase ,Cell Biology ,Plants ,Biology ,Noncoding DNA ,Additional research ,Rna regulation ,Mice ,Gene Expression Regulation ,Neoplasms ,parasitic diseases ,Animals ,Humans ,RNA Interference ,RNA, Small Interfering ,Molecular Biology ,Conserved Sequence ,Pseudogenes - Abstract
Recent significant progress toward understanding the function of pseudogenes in protozoa (Trypanosoma brucei), metazoa (mouse) and plants, make it pertinent to provide a brief overview on what has been learned about this fascinating subject. We discuss the regulatory mechanisms of pseudogenes at the post-transcriptional level and advance new ideas toward understanding the evolution of these, sometimes called "garbage genes" or "junk DNA," seeking to stimulate the interest of scientists and additional research on the subject. We hope this point-of-view can be helpful to scientists working or seeking to work on these and related issues.
- Published
- 2012
47. HITS‐CLIP: panoramic views of protein–RNA regulation in living cells
- Author
-
Robert B. Darnell
- Subjects
Regulation of gene expression ,Genetics ,High-Throughput RNA Sequencing ,Cells ,Video Recording ,Chromosome Mapping ,High-Throughput Nucleotide Sequencing ,RNA-Binding Proteins ,RNA ,Computational biology ,Biology ,Models, Biological ,Biochemistry ,Article ,Rna regulation ,HITS-CLIP ,RNA world hypothesis ,ComputingMethodologies_PATTERNRECOGNITION ,Cell Tracking ,Transcription (biology) ,Animals ,Humans ,Immunoprecipitation ,Molecular Biology - Abstract
The study of gene regulation in cells has recently begun to shift from a period dominated by the study of transcription factor-DNA interactions to a new focus on RNA regulation. This was sparked by the still-emerging recognition of the central role for RNA in cellular complexity emanating from the RNA World hypothesis, and has been facilitated by technologic advances, in particular high throughput RNA sequencing and crosslinking methods (RNA-Seq, CLIP, and HITS-CLIP). This study will place these advances in context, and, focusing on CLIP, will explain the method, what it can be used for, and how to approach using it. Examples of the successes, limitations, and future of the technique will be discussed. Copyright © 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website
- Published
- 2010
48. Integrative Modeling Defines the Nova Splicing-Regulatory Network and Its Combinatorial Controls
- Author
-
John J. Fak, Taesun Eom, Huidong Wang, Donny D. Licatalosi, Aldo Mele, Robert B. Darnell, Chaolin Zhang, Matteo Ruggiu, Christina B Marney, and Maria A. Frias
- Subjects
Nerve Tissue Proteins ,Computational biology ,Biology ,Article ,Cell Line ,Rna regulation ,Evolution, Molecular ,Mice ,Splicing factor ,Antigens, Neoplasm ,Artificial Intelligence ,Neuro-Oncological Ventral Antigen ,Animals ,Humans ,Gene Regulatory Networks ,Phosphorylation ,Oligonucleotide Array Sequence Analysis ,Genetics ,Binding Sites ,Models, Statistical ,Multidisciplinary ,Models, Genetic ,Microarray analysis techniques ,Alternative splicing ,Brain ,Computational Biology ,Proteins ,RNA-Binding Proteins ,Bayesian network ,RNA ,Bayes Theorem ,Exons ,Introns ,Alternative Splicing ,Nova (rocket) ,RNA splicing ,Nervous System Diseases ,Protein Binding - Abstract
Making the Final Cut RNA splicing, which involves selectively cutting and pasting messenger RNA to generate different proteins, is critical in regulating human physiology and diseases. However, our knowledge of the underlying rules governing splicing regulation remains incomplete. The recent emergence of next-generation sequencing and other high-throughput technologies has provided an opportunity to transform our understanding of RNA regulation. Zhang et al. (p. 439 , published online 17 June) combined multiple data sets to generate a robust and relatively complete picture of splicing regulation by the mammalian neuronal splicing factor Nova in the brain. About 700 splicing events were identified, including many novel target exons, some likely to be involved in neurological disease. Combining genomic studies with computational biology also yielded insight into the regulation of alternative splicing.
- Published
- 2010
49. Decode gene Sequence to guide Daily life
- Author
-
Ping Y and Jiaxue H
- Subjects
Posttranslational modification ,Nucleotide sequencing ,General Medicine ,Computational biology ,Epigenetics ,Gene sequence ,Biology ,Bioinformatics ,health care economics and organizations ,DNA sequencing ,Rna regulation - Abstract
Wisdom and monetary invest flushed into genetic sequencing and decoding of factors involved in temporally and spatially unfolding of zipped information in the form of nucleotide sequencing, primary, secondary and tertiary structures complicated by RNA regulation, protein modification and epigenetics. Although there are still decades or even hundreds of years ahead to make a claim that we already crack all the codes to build a life from materials like elements, small organics and inorganics, the understanding from gene sequencing already brought promise to change a daily life.
- Published
- 2015
50. Both endo-siRNAs and tRNA-derived small RNAs are involved in the differentiation of primitive eukaryote Giardia lamblia
- Author
-
Jian-You Liao, Liang-Hu Qu, Ling-Ling Zheng, Hui Zhou, Wenli Xu, Yu-Chan Zhang, Zhao-Rong Lun, Yan-Hua Guo, Yan Li, and Francisco J. Ayala
- Subjects
single-cell parasite ,Retroelements ,Evolution ,Retrotransposon ,Development ,medicine.disease_cause ,Small Interfering ,Evolution, Molecular ,Transcriptome ,Vaccine Related ,RNA, Transfer ,Genetic ,Models ,parasitic diseases ,microRNA ,medicine ,Genetics ,Giardia lamblia ,RNA, Small Interfering ,Multidisciplinary ,Genome ,Models, Genetic ,biology ,Base Sequence ,RNA ,Molecular ,High-Throughput Nucleotide Sequencing ,Biological Sciences ,biology.organism_classification ,Transfer ,NcRNA sRNA-generating region ,Transfer RNA ,Protozoan ,RNA regulation ,Nucleic Acid Conformation ,Eukaryote ,Generic health relevance ,Genome, Protozoan ,RNA, Protozoan ,Biogenesis - Abstract
Small RNAs (sRNAs), including microRNAs and endogenous siRNAs (endo-siRNAs), regulate most important biologic processes in eukaryotes, such as cell division and differentiation. Although sRNAs have been extensively studied in various eukaryotes, the role of sRNAs in the early emergence of eukaryotes is unclear. To address these questions, we deep sequenced the sRNA transcriptome of four different stages in the differentiation of Giardia lamblia, one of the most primitive eukaryotes. We identified a large number of endo-siRNAs in this fascinating parasitic protozoan and found that they were produced from live telomeric retrotransposons and three genomic regions (i.e., endo-siRNA generating regions [eSGRs]). eSGR-derived endo-siRNAs were proven to target mRNAs in trans. Gradual up-regulation of endo-siRNAs in the differentiation of Giardia suggested that they might be involved in the regulation of this process. This hypothesis was supported by the impairment of the differentiation ability of Giardia when GLDICER, essential for the biogenesis of endo-siRNAs, was knocked down. Endo-siRNAs are not the only sRNA regulators in Giardia differentiation, because a great number of tRNAs-derived sRNAs showed more dramatic expression changes than endo-siRNAs in this process. We totally identified five novel kinds of tRNAs-derived sRNAs and found that the biogenesis in four of them might be correlated with that of stress-induced tRNA-derived RNA (sitRNA), which was discovered in our previous studies. Our studies reveal an unexpected complex panorama of sRNA in G. lamblia and shed light on the origin and functional evolution of eukaryotic sRNAs.
- Published
- 2014
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.