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176 results on '"Lin, Qishan"'

1. 7SK methylation by METTL3 promotes transcriptional activity

Author

Perez-Pepe, Marcelo, Desotell, Anthony W, Li, Hengyi, Li, Wenxue, Han, Bing, Lin, Qishan, Klein, Daryl E, Liu, Yansheng, Goodarzi, Hani, and Alarcón, Claudio R

Subjects
Biochemistry and Cell Biology, Biological Sciences, Genetics, Underpinning research, 1.1 Normal biological development and functioning, Generic health relevance, Humans, Methylation, Methyltransferases, Positive Transcriptional Elongation Factor B, RNA, Small Nuclear, RNA-Binding Proteins, Transcription Factors, Transcription, Genetic
Abstract

A fundamental feature of cell signaling is the conversion of extracellular signals into adaptive transcriptional responses. The role of RNA modifications in this process is poorly understood. The small nuclear RNA 7SK prevents transcriptional elongation by sequestering the cyclin dependent kinase 9/cyclin T1 (CDK9/CCNT1) positive transcription elongation factor (P-TEFb) complex. We found that epidermal growth factor signaling induces phosphorylation of the enzyme methyltransferase 3 (METTL3), leading to METTL3-mediated methylation of 7SK. 7SK methylation enhanced its binding to heterogeneous nuclear ribonucleoproteins, causing the release of the HEXIM1 P-TEFb complex subunit1 (HEXIM1)/P-TEFb complex and inducing transcriptional elongation. Our findings establish the mechanism underlying 7SK activation and uncover a previously unknown function for the m6A modification in converting growth factor signaling events into a regulatory transcriptional response via an RNA methylation-dependent switch.

Published
2023

3. Characterization of m6A Modifiers and RNA Modifications in Uterine Fibroids.

Author

George, Jitu W, Cancino, Rosa A, Miller, Jennifer L Griffin, Qiu, Fang, Lin, Qishan, Rowley, M Jordan, Chennathukuzhi, Varghese M, and Davis, John S

Subjects
RNA modification & restriction, LIQUID chromatography-mass spectrometry, UTERINE fibroids, GENE expression, BENIGN tumors
Abstract

Uterine leiomyoma or fibroids are prevalent noncancerous tumors of the uterine muscle layer, yet their origin and development remain poorly understood. We analyzed RNA expression profiles of 15 epigenetic mediators in uterine fibroids compared to myometrium using publicly available RNA sequencing (RNA-seq) data. To validate our findings, we performed RT-qPCR on a separate cohort of uterine fibroids targeting these modifiers confirming our RNA-seq data. We then examined protein profiles of key N6-methyladenosine (m6A) modifiers in fibroids and their matched myometrium, showing no significant differences in concordance with our RNA expression profiles. To determine RNA modification abundance, mRNA and small RNA from fibroids and matched myometrium were analyzed by ultra-high performance liquid chromatography-mass spectrometry identifying prevalent m6A and 11 other known modifiers. However, no aberrant expression in fibroids was detected. We then mined a previously published dataset and identified differential expression of m6A modifiers that were specific to fibroid genetic subtype. Our analysis also identified m6A consensus motifs on genes previously identified to be dysregulated in uterine fibroids. Overall, using state-of-the-art mass spectrometry, RNA expression, and protein profiles, we characterized and identified differentially expressed m6A modifiers in relation to driver mutations. Despite the use of several different approaches, we identified limited differential expression of RNA modifiers and associated modifications in uterine fibroids. However, considering the highly heterogenous genomic and cellular nature of fibroids, and the possible contribution of single molecule m6A modifications to fibroid pathology, there is a need for greater in-depth characterization of m6A marks and modifiers in a larger and diverse patient cohort. [ABSTRACT FROM AUTHOR]

Published
2024
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7. Dynamic RNA acetylation revealed by quantitative cross-evolutionary mapping

Author

Sas-Chen, Aldema, Thomas, Justin M., Matzov, Donna, Taoka, Masato, Nance, Kellie D., Nir, Ronit, Bryson, Keri M., Shachar, Ran, Liman, Geraldy L. S., Burkhart, Brett W., Gamage, Supuni Thalalla, Nobe, Yuko, Briney, Chloe A., Levy, Michaella J., Fuchs, Ryan T., Robb, G. Brett, Hartmann, Jesse, Sharma, Sunny, Lin, Qishan, Florens, Laurence, Washburn, Michael P., Isobe, Toshiaki, Santangelo, Thomas J., Shalev-Benami, Moran, Meier, Jordan L., and Schwartz, Schraga

Published
2020
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14. 7SK methylation Promotes Transcriptional Activity

Author

Perez-Pepe, Marcelo, primary, Desotell, Anthony W., additional, Li, Hengyi, additional, Li, Wenxue, additional, Han, Bing, additional, Lin, Qishan, additional, Klein, Daryl E., additional, Liu, Yansheng, additional, Goodarzi, Hani, additional, and Alarcón, Claudio R., additional

Published
2022
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15. Disease-associated inosine misincorporation into RNA hinders translation

Author

Schroader, Jacob H, primary, Jones, Lindsey A, additional, Meng, Ryan, additional, Shorrock, Hannah K, additional, Richardson, Jared I, additional, Shaughnessy, Sharon M, additional, Lin, Qishan, additional, Begley, Thomas J, additional, Berglund, J Andrew, additional, Fuchs, Gabriele, additional, Handley, Mark T, additional, and Reddy, Kaalak, additional

Published
2022
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19. Friedreich cardiomyopathy is a desminopathy

Author

Koeppen, Arnulf H., Rafique, Rahman F., Mazurkiewicz, Joseph E., Pelech, Steven, Sutter, Catherine, Lin, Qishan, and Qian, Jiang

Subjects
Original Paper
Abstract

Heart disease is an integral part of Friedreich ataxia (FA) and the most common cause of death in this autosomal recessive disease. The result of the mutation is lack of frataxin, a small mitochondrial protein. The clinical and pathological phenotypes of FA are complex, involving brain, spinal cord, dorsal root ganglia, sensory nerves, heart, and endocrine pancreas. The hypothesis is that frataxin deficiency causes downstream changes in the proteome of the affected tissues, including the heart. A proteomic analysis of heart proteins in FA cardiomyopathy by antibody microarray, Western blots, immunohistochemistry, and double-label laser scanning confocal immunofluorescence microscopy revealed upregulation of desmin and its chaperone protein, αB-crystallin. In normal hearts, these two proteins are co-localized at intercalated discs and Z discs. In FA, desmin and αB-crystallin aggregate, causing chaotic modification of intercalated discs, clustering of mitochondria, and destruction of the contractile apparatus of cardiomyocytes. Western blots of tissue lysates in FA cardiomyopathy reveal a truncated desmin isoprotein that migrates at a lower molecular weight range than wild type desmin. While desmin and αB-crystallin are not mutated in FA, the accumulation of these proteins in FA hearts allows the conclusion that FA cardiomyopathy is a desminopathy akin to desmin myopathy of skeletal muscle.

Published
2021

25. Characterization of m6A Modifiers and RNA Modifications in Uterine Fibroids

Author

George, Jitu W, Cancino, Rosa A, Griffin Miller, Jennifer L, Qiu, Fang, Lin, Qishan, Rowley, M Jordan, Chennathukuzhi, Varghese M, and Davis, John S

Abstract

Uterine leiomyoma or fibroids are prevalent noncancerous tumors of the uterine muscle layer, yet their origin and development remain poorly understood. We analyzed RNA expression profiles of 15 epigenetic mediators in uterine fibroids compared to myometrium using publicly available RNA sequencing (RNA-seq) data. To validate our findings, we performed RT-qPCR on a separate cohort of uterine fibroids targeting these modifiers confirming our RNA-seq data. We then examined protein profiles of key N6-methyladenosine (m6A) modifiers in fibroids and their matched myometrium, showing no significant differences in concordance with our RNA expression profiles. To determine RNA modification abundance, mRNA and small RNA from fibroids and matched myometrium were analyzed by ultra-high performance liquid chromatography-mass spectrometry identifying prevalent m6A and 11 other known modifiers. However, no aberrant expression in fibroids was detected. We then mined a previously published dataset and identified differential expression of m6A modifiers that were specific to fibroid genetic subtype. Our analysis also identified m6A consensus motifs on genes previously identified to be dysregulated in uterine fibroids. Overall, using state-of-the-art mass spectrometry, RNA expression, and protein profiles, we characterized and identified differentially expressed m6A modifiers in relation to driver mutations. Despite the use of several different approaches, we identified limited differential expression of RNA modifiers and associated modifications in uterine fibroids. However, considering the highly heterogenous genomic and cellular nature of fibroids, and the possible contribution of single molecule m6A modifications to fibroid pathology, there is a need for greater in-depth characterization of m6A marks and modifiers in a larger and diverse patient cohort.

Published
2024
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30. Membrane lipids have multiple effects on interfacial catalysis by a phosphatidic acid-preferring phospholipase A1 from bovine testis

Author

Lin, Qishan, Higgs, Henry N., and Glomset, John A.

Subjects
Phospholipases -- Research, Membrane lipids -- Research, Biological sciences, Chemistry
Abstract

The stability, activity, and specificity of a cytosolic phospholipase A1 from bovine testis depends on the composition of membrane lipids. Manipulating the composition of membrane lipids increased its affinity for phosphatidic acid.

Published
2000

31. Translational offsetting as a mode of estrogen receptor α‐dependent regulation of gene expression

Author

Lorent, Julie, Kusnadi, Eric P, Hoef, Vincent, Rebello, Richard J, Leibovitch, Matthew, Ristau, Johannes, Chen, Shan, Lawrence, Mitchell G, Szkop, Krzysztof J, Samreen, Baila, Balanathan, Preetika, Rapino, Francesca, Close, Pierre, Bukczynska, Patricia, Scharmann, Karin, Takizawa, Itsuhiro, Risbridger, Gail P, Selth, Luke A, Leidel, Sebastian A, Lin, Qishan, Topisirovic, Ivan, Larsson, Ola, and Furic, Luc

Subjects
540 Chemistry, 570 Life sciences, biology
Abstract

Estrogen receptor alpha (ERα) activity is associated with increased cancer cell proliferation. Studies aiming to understand the impact of ERα on cancer-associated phenotypes have largely been limited to its transcriptional activity. Herein, we demonstrate that ERα coordinates its transcriptional output with selective modulation of mRNA translation. Importantly, translational perturbations caused by depletion of ERα largely manifest as "translational offsetting" of the transcriptome, whereby amounts of translated mRNAs and corresponding protein levels are maintained constant despite changes in mRNA abundance. Transcripts whose levels, but not polysome association, are reduced following ERα depletion lack features which limit translation efficiency including structured 5'UTRs and miRNA target sites. In contrast, mRNAs induced upon ERα depletion whose polysome association remains unaltered are enriched in codons requiring U34-modified tRNAs for efficient decoding. Consistently, ERα regulates levels of U34-modifying enzymes and thereby controls levels of U34-modified tRNAs. These findings unravel a hitherto unprecedented mechanism of ERα-dependent orchestration of transcriptional and translational programs that may be a pervasive mechanism of proteome maintenance in hormone-dependent cancers.

Published
2019
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32. Translational offsetting as a mode of estrogen receptor α‐dependent regulation of gene expression

Author

Lorent, Julie, primary, Kusnadi, Eric P, additional, Hoef, Vincent, additional, Rebello, Richard J, additional, Leibovitch, Matthew, additional, Ristau, Johannes, additional, Chen, Shan, additional, Lawrence, Mitchell G, additional, Szkop, Krzysztof J, additional, Samreen, Baila, additional, Balanathan, Preetika, additional, Rapino, Francesca, additional, Close, Pierre, additional, Bukczynska, Patricia, additional, Scharmann, Karin, additional, Takizawa, Itsuhiro, additional, Risbridger, Gail P, additional, Selth, Luke A, additional, Leidel, Sebastian A, additional, Lin, Qishan, additional, Topisirovic, Ivan, additional, Larsson, Ola, additional, and Furic, Luc, additional

Published
2019
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35. A systems chemoproteomic analysis of acyl-CoA/protein interaction networks

Author

Levy, Michaella J., primary, Montgomery, David C., additional, Sardiu, Mihaela E., additional, Bergholtz, Sarah E., additional, Nance, Kellie D., additional, Montano, Jose, additional, Thorpe, Abigail L., additional, Fox, Stephen D., additional, Lin, Qishan, additional, Andresson, Thorkell, additional, Florens, Laurence, additional, Washburn, Michael P., additional, and Meier, Jordan L., additional

Published
2019
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40. Existing drugs as broad-spectrum and potent inhibitors for Zika virus by targeting NS2B-NS3 interaction

Author

Li, Zhong, primary, Brecher, Matthew, additional, Deng, Yong-Qiang, additional, Zhang, Jing, additional, Sakamuru, Srilatha, additional, Liu, Binbin, additional, Huang, Ruili, additional, Koetzner, Cheri A, additional, Allen, Christina A, additional, Jones, Susan A, additional, Chen, Haiying, additional, Zhang, Na-Na, additional, Tian, Min, additional, Gao, Fengshan, additional, Lin, Qishan, additional, Banavali, Nilesh, additional, Zhou, Jia, additional, Boles, Nathan, additional, Xia, Menghang, additional, Kramer, Laura D, additional, Qin, Cheng-Feng, additional, and Li, Hongmin, additional

Published
2017
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43. Refolding of a fully functional flavivirus methyltransferase revealed that S-adenosyl methionine but not S-adenosyl homocysteine is copurified with flavivirus methyltransferase

Author

Brecher, Matthew B, Li, Zhong, Zhang, Jing, Chen, Hui, Lin, Qishan, Liu, Binbin, and Li, Hongmin

Subjects
Models, Molecular, S-Adenosylmethionine, viruses, virus diseases, Methyltransferases, Dengue Virus, Crystallography, X-Ray, S-Adenosylhomocysteine, Protein Refolding, Dengue, Full-Length Papers, Humans, West Nile virus, West Nile Fever
Abstract

Methylation of flavivirus RNA is vital for its stability and translation in the infected host cell. This methylation is mediated by the flavivirus methyltransferase (MTase), which methylates the N7 and 2'-O positions of the viral RNA cap by using S-adenosyl-l-methionine (SAM) as a methyl donor. In this report, we demonstrate that SAM, in contrast to the reaction by-product S-adenosyl-l-homocysteine, which was assumed previously, is copurified with the Dengue (DNV) and West Nile virus MTases produced in Escherichia coli (E. coli). This endogenous SAM can be removed by denaturation and refolding of the MTase protein. The refolded MTase of DNV serotype 3 (DNV3) displays methylation activity comparable to native enzyme, and its crystal structure at 2.1 Å is almost identical to that of native MTase. We characterized the binding of Sinefungin (SIN), a previously described SAM-analog inhibitor of MTase function, to the native and refolded DNV3 MTase by isothermal titration calorimetry, and found that SIN binds to refolded MTase with more than 16 times the affinity of SIN binding to the MTase purified natively. Moreover, we show that SAM is also copurified with other flavivirus MTases, indicating that purification by refolding may be a generally applicable tool for studying flavivirus MTase inhibition.

Published
2014

46. Hyperinsulinemia enhances interleukin-17-induced inflammation to promote prostate cancer development in obese mice through inhibiting glycogen synthase kinase 3-mediated phosphorylation and degradation of interleukin-17 receptor

Author

Liu, Sen, primary, Zhang, Qiuyang, additional, Chen, Chong, additional, Ge, Dongxia, additional, Qu, Yine, additional, Chen, Rongyi, additional, Fan, Yi-Ming, additional, Li, Nan, additional, Tang, Wendell W., additional, Zhang, Wensheng, additional, Zhang, Kun, additional, Wang, Alun R., additional, Rowan, Brian G., additional, Hill, Steven M., additional, Sartor, Oliver, additional, Abdel-Mageed, Asim B., additional, Myers, Leann, additional, Lin, Qishan, additional, and You, Zongbing, additional

Published
2016
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47. Rapid Analysis of Intact Protein Using Liquid Chromatography Coupled with Mass Spectrometry

Author

Lin, Qishan and Zhu, Jinghua

Subjects
Scientific Poster Abstracts
Abstract

Nearly every process conducted in a biotechnology company requires a tremendous amount of analytical characterization in support of the development of biopharmaceutical products. Because of the inherent complexity of bio-therapeutics, characterization of these large bio-molecules such as proteins, antibodies is more significantly challenging than it is for small molecules. Therefore, numerous instrumental methods are applied in order to fully characterization these high-molecular-weight products. Intact protein mass measurement becomes a routine practice for quality control and comparability studies during manufacturing changes. This research sought to develop a fast, robust workflow for accurate, highly sensitive intact protein mass measurements using liquid chromatography coupled with time-of-flight mass spectrometer. The workflow included an on-line trapping column packed with 10 μm poly (Styrene-Divinylbenzene) particles (POROS® R1) with 4000 angstrom pore size for desalting and a column heater to increase mass transfer and diffusion. We showed examples of the MS measurements of antibodies as well as over-expressed human serum albumin. This method could easily be adapted to any core facilities that provide services regarding intact protein MS measurement.

Published
2012

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