Pre-mRNA processing factors meet the DNA damage response
Open accessAbstract
It is well-known that DNA-damaging agents induce genome instability, but only recently have we begun to appreciate that chromosomes are fragile per se and frequently subject to DNA breakage. DNA replication further magnifies such fragility, because it leads to accumulation of single-stranded DNA. Recent findings suggest that chromosome fragility is similarly increased during transcription. Transcripts produced by RNA polymerase II (RNAPII) are subject to multiple processing steps, including maturation of 5' and 3' ends and splicing, followed by transport to the cytoplasm. RNA maturation starts on nascent transcripts and is mediated by a number of diverse proteins and ribonucleoprotein particles some of which are recruited cotranscriptionally through interactions with the carboxy-terminal domain of RNAPII. This coupling is thought to maximize efficiency of pre-mRNA maturation and directly impacts the choice of alternative splice sites. Mounting evidence suggests that lack of coordination among different RNA maturation steps, by perturbing the interaction of nascent transcripts with the DNA template, has deleterious effects on genome stability. Thus, in the absence of proper surveillance mechanisms, transcription could be a major source of DNA damage in cancer. Recent high-throughput screenings in human cells and budding yeast have identified several factors implicated in RNA metabolism that are targets of DNA damage checkpoint kinases: ATM (ataxia telangiectasia mutated) and ATR (ATM-Rad3 related) (Tel1 and Mec1 in budding yeast, respectively). Moreover, inactivation of various RNA processing factors induces accumulation of γH2AX foci, an early sign of DNA damage. Thus, a complex network is emerging that links DNA repair and RNA metabolism. In this review we provide a comprehensive overview of the role played by pre-mRNA processing factors in the cell response to DNA damage and in the maintenance of genome stability.
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Several mRNA 3′ end processing factors and RNA-binding proteins, such as CPSF2, ZFP36L2, and SRSF7, were identified among cisplatin sensitization hits.
“In addition, in agreement with the importance of pre-mRNA processing factors in the DNA damage response46, several mRNA 3′ end processing factors and RNA-binding proteins were identified, such as CPSF2, ZFP36L2, and SRSF7.”
From Large-scale CRISPR screening in primary human 3D gastric organoids enables comprehensive dissection of gene-drug interactions (2025) · cites this paper as [46]
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Molecular mechanisms of etoposide
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- Authors
- Montecucco, A., & Biamonti, G.
- Affiliations
- Istituto di Genetica Molecolare (IT)
- Corresponding author
- Montecucco, Alessandra
- Biamonti, Giuseppe
- Venue
- Frontiers in Genetics
- Publisher
- Frontiers Media SA
- Published
- 2013
- Volume
- 4
- Pages
- 102-102
- ISSN
- 1664-8021 (ISSN-L)
- PMC
- PMC3674313
- OpenAlex
- W2034847678
- Cited by
- 69
- References
- 121
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 6 · 2020: 2 · 2019: 5 · 2018: 7 · 2017: 6 · 2016: 6 · 2015: 12 · 2014: 7 · 2013: 4
- FWCI
- 4.33
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Genetics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Ministero dell’Istruzione, dell’Università e della Ricerca (PNR-CNR Aging Program 2012–2014)
- Associazione Italiana per la Ricerca sul Cancro
- Topics
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- pre-mRNA processing, DNA damage response, genome stability, RNA polymerase II, C-terminal domain, alternative splicing, RNA processing, ATM, ATR, Tel1, Mec1, γH2AX foci, DNA repair, RNA metabolism
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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