Elongation Factor TFIIS Prevents Transcription Stress and R-Loop Accumulation to Maintain Genome Stability
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Although correlations between RNA polymerase II (RNAPII) transcription stress, R-loops, and genome instability have been established, the mechanisms underlying these connections remain poorly understood. Here, we used a mutant version of the transcription elongation factor TFIIS (TFIIS mut ), aiming to specifically induce increased levels of RNAPII pausing, arrest, and/or backtracking in human cells. Indeed, TFIIS mut expression results in slower elongation rates, relative depletion of polymerases from the end of genes, and increased levels of stopped RNAPII; it affects mRNA splicing and termination as well. Remarkably, TFIIS mut expression also dramatically increases R-loops, which may form at the anterior end of backtracked RNAPII and trigger genome instability, including DNA strand breaks. These results shed light on the relationship between transcription stress and R-loops and suggest that different classes of R-loops may exist, potentially with distinct consequences for genome stability.
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Slowing down transcription using mutants of the elongation factor TFIIS shifts termination upstream.
“Consistent with the results obtained with slow RNA Pol II mutants, slowing‐down transcription using mutants of the elongation factor TFIIS also shifts termination upstream (Sheridan et al, 2019; Zatreanu et al, 2019).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Zatreanu et al, 2019
TFIIS increases RNA Pol II speed in human cells.
“Accordingly, TFIIS increases RNA Pol II speed in human cells (Sheridan et al, 2019; Zatreanu et al, 2019), while its deletion had no effect on RNA Pol II velocity in budding yeast (Mason & Struhl, 2005).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Zatreanu et al, 2019
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- Authors
- Zatreanu, D., Han, Z., Mitter, R., Tumini, E., Williams, H., Gregersen, L., Dirac-Svejstrup, A. B., Roma, S., Stewart, A., Aguilera, A., & Svejstrup, J. Q.
- Affiliations
- The Francis Crick Institute (GB)
- Consejo Superior de Investigaciones Científicas (ES)
- Corresponding author
- Svejstrup, Jesper Q.
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2019-10
- Volume
- 76
- Issue
- 1
- Pages
- 57-69.e9
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC6863433
- OpenAlex
- W2973185164
- Cited by
- 124
- References
- 63
- Citations by year
- 2026: 13 · 2025: 23 · 2024: 20 · 2023: 13 · 2022: 20 · 2021: 22 · 2020: 12 · 2019: 1
- FWCI
- 4.53
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, cc-by-nc-nd)
- RISalud Institutional Health Repository of Andalucía (submittedVersion, cc-by)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by)
- Figshare (submittedVersion, cc-by)
- Deposito de Investigacion Universidad de Sevilla (University of Seville) (submittedVersion, cc-by-nc-nd)
- Funders
- European Research Council
- Francis Crick Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- TFIIS, transcription elongation, RNA polymerase II pausing, R-loops, genome stability, backtracking, DNA strand breaks, mRNA splicing, transcription termination
- MeSH terms
- R-Loop Structures, Humans, Mutation, RNA Polymerase II, RNA Splicing, RNA, Messenger, Stress, Physiological, Structure-Activity Relationship, Transcription, Genetic, Transcriptional Elongation Factors, Genomic Instability, Cell Line, Tumor, HEK293 Cells
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