Cited by 131Genomics and Chromatin DynamicsChromatin Remodeling and CancerRNA Research and Splicing

Paf1C regulates RNA polymerase II progression by modulating elongation rate

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Hou, Liming, Wang, Yating, Liu, Yu, Zhang, Nan, Shamovsky, Ilya, Nudler, Evgeny, Tian, Bin, Dynlacht, Brian David·2019·Proceedings of the National Academy of Sciences

Abstract

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.

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  • Paf1C specifically increases RNA Pol II velocity within the first part of gene bodies in mice.

    “Paf1C specifically increases RNA Pol II velocity within the first part of gene bodies in mice (Hou et al, 2019), although no effect of the loss of this factor could be measured in budding yeast (Mason & Struhl, 2005).”

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Authors
Hou, L., Wang, Y., Liu, Y., Zhang, N., Shamovsky, I., Nudler, E., Tian, B., & Dynlacht, B. D.
Affiliations
  • NYU Langone Health (US)
  • Rutgers New Jersey Medical School (US)
  • New York University (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Dynlacht, Brian David
Venue
Proceedings of the National Academy of Sciences
Published
2019-06-28
Volume
116
Issue
29
Pages
14583-14592
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2955819370
Cited by
129
References
53
Citations by year
2026: 11 · 2025: 13 · 2024: 20 · 2023: 21 · 2022: 18 · 2021: 22 · 2020: 22 · 2019: 2
FWCI
5.29
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
NIH (R01GM122395, R01GM126891)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Keywords
Paf1C, RNA polymerase II, transcription elongation, elongation rate, Ser5 phosphorylation, histone H2B ubiquitylation, nascent RNA, early termination, Spt5, Spt6, FACT complex, gene body, conditional gene deletion
MeSH terms
Animals, Carrier Proteins, Cell Line, Histones, Promoter Regions, Genetic, RNA Polymerase II, Myoblasts, RNA, Small Interfering, Mice, Ubiquitination, Gene Knockout Techniques, Transcription Elongation, Genetic, Transcription Termination, Genetic, CRISPR-Cas Systems

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