RECQL5 Controls Transcript Elongation and Suppresses Genome Instability Associated with Transcription Stress
Open accessAbstract
RECQL5 is the sole member of the RECQ family of helicases associated with RNA polymerase II (RNAPII). We now show that RECQL5 is a general elongation factor that is important for preserving genome stability during transcription. Depletion or overexpression of RECQL5 results in corresponding shifts in the genome-wide RNAPII density profile. Elongation is particularly affected, with RECQL5 depletion causing a striking increase in the average rate, concurrent with increased stalling, pausing, arrest, and/or backtracking (transcription stress). RECQL5 therefore controls the movement of RNAPII across genes. Loss of RECQL5 also results in the loss or gain of genomic regions, with the breakpoints of lost regions located in genes and common fragile sites. The chromosomal breakpoints overlap with areas of elevated transcription stress, suggesting that RECQL5 suppresses such stress and its detrimental effects, and thereby prevents genome instability in the transcribed region of genes.
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Decreasing RNA Pol II speed smoothens transcription elongation and renders RNA Pol II less prone to pausing and arrest which can induce transcription stress.
“The hypothesis behind these two observations is that decreasing RNA Pol II speed smoothens transcription elongation and thus renders RNA Pol II less prone to pausing and arrest which can induce transcription stress (Saponaro et al, 2014).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Saponaro et al, 2014
In the Discussion (“RECQL5, a General RNAPII Elongation Factor”), the authors propose that RECQL5 may smooth or buffer elongation, producing a slower but less interrupted process. The Results (“RECQL5-Related Transcription Stress”) also link RECQL5 depletion to faster elongation and more pausing or arrest. The paper does not establish that decreasing RNAPII speed itself causes the smoother elongation described in the citing sentence. (LLM, conf=0.82)
Experimental — accuracy not yet measuredFactors regulating RNA Pol II velocity play an essential role in cells.
“Factors regulating RNA Pol II velocity therefore play an essential role in cells and are the topic of several recent studies using genome‐wide RNA Pol II speed measurement methods (Table 2) (Saponaro et al, 2014; Liang et al, 2018; Baluapuri et al, 2019; Cortazar et al, 2019; Gregersen et al, 2019; Hou et al, 2019; Sheridan et al, 2019; Fan et al, 2020).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Saponaro et al, 2014
RECQL5 decreases RNA Pol II speed and suppresses genome instability.
“Finally, RECQL5, a member of the conserved family of RECQ DNA helicases, decreases RNA Pol II speed and suppresses genome instability (Saponaro et al, 2014).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Saponaro et al, 2014
In mammalian cells most studies only consider very long genes to accurately decipher an elongation speed.
“Indeed, in mammalian cells most studies only consider very long genes to accurately decipher an elongation speed (Saponaro et al, 2014; Cortazar et al, 2019; Gregersen et al, 2019; Hou et al, 2019; Sheridan et al, 2019; Fan et al, 2020).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Saponaro et al, 2014
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References 47 · Cited by 207
- Authors
- Saponaro, M., Kantidakis, T., Mitter, R., Kelly, G. P., Heron, M., Williams, H., Söding, J., Stewart, A., & Svejstrup, J. Q.
- Affiliations
- Cancer Research UK (GB)
- Center for Integrated Protein Science Munich (DE)
- Corresponding author
- Svejstrup, Jesper Q.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2014-05
- Volume
- 157
- Issue
- 5
- Pages
- 1037-1049
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4032574
- OpenAlex
- W2022064170
- Cited by
- 207
- References
- 47
- Citations by year
- 2026: 11 · 2025: 13 · 2024: 19 · 2023: 18 · 2022: 8 · 2021: 22 · 2020: 27 · 2019: 23 · 2018: 11 · 2017: 15 · 2016: 20 · 2015: 11 · 2014: 9
- FWCI
- 7.52
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Cell (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Aston Publications Explorer (Aston University) (acceptedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, cc-by)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Funders
- Cancer Research UK (11567)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- 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
- Keywords
- RECQL5, RecQ helicase, RNA polymerase II, transcription elongation, genomic instability, common fragile sites, chromosomal breakpoints, backtracking
- MeSH terms
- Humans, RNA Polymerase II, Transcription, Genetic, Genome, Human, Genomic Instability, RecQ Helicases, HEK293 Cells, Transcription Elongation, Genetic
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