globalchange  > 气候变化与战略
DOI: 10.1073/pnas.1904324116
论文题名:
Paf1C regulates RNA polymerase II progression by modulating elongation rate
作者: Hou L.; Wang Y.; Liu Y.; Zhang N.; Shamovsky I.; Nudler E.; Tian B.; Dynlacht B.D.
刊名: Proceedings of the National Academy of Sciences of the United States of America
ISSN: 0027-8424
出版年: 2019
卷: 116, 期:29
起始页码: 14583
结束页码: 14592
语种: 英语
英文关键词: Nucleosome occupancy ; Paf1 complex ; RNA polymerase II ; Transcription elongation rate
Scopus关键词: elongation factor ; elongation factor Paf1C ; RNA polymerase II ; unclassified drug ; 3' untranslated region ; animal cell ; animal experiment ; Article ; controlled study ; CRISPR Cas system ; down regulation ; gene loss ; histone ubiquitination ; mass spectrometry ; mouse ; nonhuman ; nucleosome ; polyadenylation ; priority journal ; promoter region ; protein function ; protein phosphorylation ; proteomics ; signal transduction ; transcription elongation ; ubiquitination ; upregulation
英文摘要: Elongation factor Paf1C regulates several stages of the RNA polymerase II (Pol II) transcription cycle, although it is unclear how it modulates Pol II distribution and progression in mammalian cells. We found that conditional ablation of Paf1 resulted in the accumulation of unphosphorylated and Ser5 phosphorylated Pol II around promoter-proximal regions and within the first 20 to 30 kb of gene bodies, respectively. Paf1 ablation did not impact the recruitment of other key elongation factors, namely, Spt5, Spt6, and the FACT complex, suggesting that Paf1 function may be mechanistically distinguishable from each of these factors. Moreover, loss of Paf1 triggered an increase in TSS-proximal nucleosome occupancy, which could impose a considerable barrier to Pol II elongation past TSS-proximal regions. Remarkably, accumulation of Ser5P in the first 20 to 30 kb coincided with reductions in histone H2B ubiquitylation within this region. Furthermore, we show that nascent RNA species accumulate within this window, suggesting a mechanism whereby Paf1 loss leads to aberrant, prematurely terminated transcripts and diminution of full-length transcripts. Importantly, we found that loss of Paf1 results in Pol II elongation rate defects with significant rate compression. Our findings suggest that Paf1C is critical for modulating Pol II elongation rates by functioning beyond the pause-release step as an “accelerator” over specific early gene body regions. © 2019 National Academy of Sciences. All rights reserved.
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资源类型: 期刊论文
标识符: http://119.78.100.158/handle/2HF3EXSE/163611
Appears in Collections:气候变化与战略

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作者单位: Hou, L., Department of Pathology, New York University School of Medicine, New York, NY 10016, United States, Perlmutter Cancer Institute, New York University School of Medicine, New York, NY 10016, United States; Wang, Y., Department of Pathology, New York University School of Medicine, New York, NY 10016, United States, Perlmutter Cancer Institute, New York University School of Medicine, New York, NY 10016, United States; Liu, Y., Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ 07103, United States; Zhang, N., Department of Pathology, New York University School of Medicine, New York, NY 10016, United States, Perlmutter Cancer Institute, New York University School of Medicine, New York, NY 10016, United States; Shamovsky, I., Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, United States; Nudler, E., Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, United States, Howard Hughes Medical Institute, New York University School of Medicine, New York, NY 10016, United States; Tian, B., Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ 07103, United States; Dynlacht, B.D., Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ 07103, United States

Recommended Citation:
Hou L.,Wang Y.,Liu Y.,et al. Paf1C regulates RNA polymerase II progression by modulating elongation rate[J]. Proceedings of the National Academy of Sciences of the United States of America,2019-01-01,116(29)
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