Cited by 124Genomics and Chromatin DynamicsDNA Repair MechanismsRNA Research and Splicing

Elongation Factor TFIIS Prevents Transcription Stress and R-Loop Accumulation to Maintain Genome Stability

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Zatreanu, Diana, Han, Zhong, Mitter, Richard, Tumini, Emanuela, Williams, Hannah, Gregersen, Lea, Dirac-Svejstrup, A. Barbara, Roma, Stefania +3 more·2019·Molecular Cell

Abstract

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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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.
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2019-10
Volume
76
Issue
1
Pages
57-69.e9
ISSN
1097-2765 (ISSN-L)
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
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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