Stable Pausing by RNA Polymerase II Provides an Opportunity to Target and Integrate Regulatory Signals
Open accessAbstract
Metazoan gene expression is often regulated after the recruitment of RNA polymerase II (Pol II) to promoters, through the controlled release of promoter-proximally paused Pol II into productive RNA synthesis. Despite the prevalence of paused Pol II, very little is known about the dynamics of these early elongation complexes or the fate of the short transcription start site-associated (tss) RNAs they produce. Here, we demonstrate that paused elongation complexes can be remarkably stable, with half-lives exceeding 15 min at genes with inefficient pause release. Promoter-proximal termination by Pol II is infrequent, and released tssRNAs are targeted for rapid degradation. Further, we provide evidence that the predominant tssRNA species observed are nascent RNAs held within early elongation complexes. We propose that stable pausing of polymerase provides a temporal window of opportunity for recruitment of factors to modulate gene expression and that the nascent tssRNA represents an appealing target for these interactions.
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Inhibition of P-TEFb and thus repression of the release of RNA Pol II from promoter-proximal pausing blocks transcription of almost all genes.
“Inhibition of P‐TEFb and thus repression of the release of RNA Pol II from promoter‐proximal pausing has been shown to block transcription of almost all genes (Henriques et al, 2013; Jonkers et al, 2014).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Henriques et al, 2013
The Results section (‘Blocking pause release leads to accumulation of promoter Pol II’; page not provided) reports that P-TEFb inhibition prevents paused Pol II from moving downstream and traps it near the promoters of many genes. It does not establish that transcription is blocked at almost all genes; it says the least-expressed, highly paused genes were largely unaffected by the brief treatment. (LLM, conf=0.88)
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References 46 · Cited by 240
- Authors
- Henriques, T., Gilchrist, D. A., Nechaev, S., Bern, M., Muse, G. W., Burkholder, A., Fargo, D. C., & Adelman, K.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Adelman, Karen
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2013-11
- Volume
- 52
- Issue
- 4
- Pages
- 517-528
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC3845087
- OpenAlex
- W2078531707
- Cited by
- 240
- References
- 46
- Citations by year
- 2026: 7 · 2025: 14 · 2024: 20 · 2023: 12 · 2022: 19 · 2021: 25 · 2020: 20 · 2019: 24 · 2018: 30 · 2017: 21 · 2016: 13 · 2015: 25 · 2014: 10
- FWCI
- 7.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (P40OD010949)
- National Institute of Environmental Health Sciences (ZIAES101987, Z01ES101987)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- RNA polymerase II pausing, promoter-proximal pausing, nascent RNA, pause release, transcriptional regulation
- MeSH terms
- Animals, Base Sequence, Cell Line, Chromatin, Drosophila melanogaster, Gene Expression Regulation, Promoter Regions, Genetic, RNA Polymerase II, Signal Transduction, RNA, Small Cytoplasmic, RNA Stability, Drosophila Proteins, Transcription Elongation, Genetic, Exosome Multienzyme Ribonuclease Complex
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