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Structural basis of RNA polymerase II backtracking, arrest and reactivation
Open accessAbstract
During gene transcription, RNA polymerase (Pol) II moves forwards along DNA and synthesizes messenger RNA. However, at certain DNA sequences, Pol II moves backwards, and such backtracking can arrest transcription. Arrested Pol II is reactivated by transcription factor IIS (TFIIS), which induces RNA cleavage that is required for cell viability. Pol II arrest and reactivation are involved in transcription through nucleosomes and in promoter-proximal gene regulation. Here we present X-ray structures at 3.3 Å resolution of an arrested Saccharomyces cerevisiae Pol II complex with DNA and RNA, and of a reactivation intermediate that additionally contains TFIIS. In the arrested complex, eight nucleotides of backtracked RNA bind a conserved 'backtrack site' in the Pol II pore and funnel, trapping the active centre trigger loop and inhibiting mRNA elongation. In the reactivation intermediate, TFIIS locks the trigger loop away from backtracked RNA, displaces RNA from the backtrack site, and complements the polymerase active site with a basic and two acidic residues that may catalyse proton transfers during RNA cleavage. The active site is demarcated from the backtrack site by a 'gating tyrosine' residue that probably delimits backtracking. These results establish the structural basis of Pol II backtracking, arrest and reactivation, and provide a framework for analysing gene regulation during transcription elongation.
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“Backtracked RNA Pol II can be rescued by the elongation factor TFIIS which stimulates RNA Pol II intrinsic cleavage activity (Cheung & Cramer, 2011).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Cheung & Cramer, 2011
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Cramer, P. (2019) · Nature · doi:10.1038/s41586-019-1517-4 · Cited by 793
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Control of Transcriptional Elongation
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Metadata
- Authors
- Cheung, A. C. M., & Cramer, P.
- Affiliations
- Ludwig-Maximilians-Universität München (DE)
- Max Planck Society (DE)
- Corresponding author
- Cramer, Patrick
- Venue
- Nature
- Published
- 2011-02-23
- Volume
- 471
- Issue
- 7337
- Pages
- 249-253
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2036166114
- Cited by
- 373
- References
- 31
- Citations by year
- 2026: 15 · 2025: 20 · 2024: 21 · 2023: 23 · 2022: 27 · 2021: 28 · 2020: 15 · 2019: 37 · 2018: 20 · 2017: 29 · 2016: 25 · 2015: 15 · 2014: 23 · 2013: 33 · 2012: 25
- FWCI
- 12.68
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DORA PSI (Paul Scherrer Institute) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Max Planck Digital Library (submittedVersion)
- GRO (submittedVersion, cc-by)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Explore Bristol Research (submittedVersion)
- Bristol Research (University of Bristol) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- RNA polymerase II, backtracking, transcription arrest, TFIIS, transcription elongation, Saccharomyces cerevisiae, crystal structure, trigger loop, RNA cleavage, nucleosome, transcription factor binding sites, polymerase active site, nucleotide binding site
- MeSH terms
- Enzyme Activation, Models, Biological, Models, Molecular, Movement, Protons, RNA Polymerase II, Saccharomyces cerevisiae, Structure-Activity Relationship, Tyrosine, Protein Structure, Tertiary, Crystallography, X-Ray, Catalytic Domain, Protein Subunits, Transcriptional Elongation Factors, Biocatalysis
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