Control of Gene Expression in Senescence through Transcriptional Read-Through of Convergent Protein-Coding Genes
Open accessAbstract
Antisense RNAs are non-coding RNAs that can regulate their corresponding sense RNAs and are generally produced from specific promoters. We uncover here a family of antisense RNAs, named START RNAs, produced during cellular senescence by transcriptional read-through at convergent protein-coding genes. Importantly, START RNAs repress the expression of their corresponding sense RNAs. In proliferative cells, we found that the Pol II elongation rate is limited downstream of TTS at START loci, allowing transcription termination to occur before Pol II reaches the convergent genes, thus preventing antisense RNA production and interference with the expression of the convergent genes. START RNAs are repressed by H2A.Z histone variant, whose local occupancy decreases in senescence. Our results thus uncover a mechanism of gene expression regulation relying on read-through antisense transcript production at convergent genes, underlining the functional importance of chromatin regulation in the control of RNA pol II elongation rate at intergenic regions.
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Transcription speed increases downstream of two genes in response to activation of an oncogene and correlates with an increase in transcriptional read-through downstream of these genes.
“Interestingly, we recently showed that transcription speed increases downstream of two genes in response to activation of an oncogene and that this increase correlates with an increase in transcriptional read‐though downstream of these genes (Muniz et al, 2017).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Muniz et al, 2017
The increase in RNA Pol II velocity downstream of genes is accompanied by an increase in transcriptional read-through which interferes with and thus decreases the expression of downstream convergent protein-coding genes.
“Moreover, we have shown that the increase in RNA Pol II velocity downstream of genes is accompanied by an increase in transcriptional read‐through which interferes with and thus decreases the expression of downstream convergent protein‐coding genes (Muniz et al, 2017).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Muniz et al, 2017
Transcription speed increases downstream of some protein-coding genes in response to an oncogenic signal.
“Third, transcription speed increases downstream of some protein‐coding genes in response to an oncogenic signal (Muniz et al, 2017).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Muniz et al, 2017
Convergent genes, antisense to the transcriptional read-through induced in response to oncogene-induced senescence, are enriched in pro-proliferative genes.
“Indeed, we have shown that those convergent genes, antisense to the transcriptional read‐through induced in response to oncogene‐induced senescence, are enriched in pro‐proliferative genes (Muniz et al, 2017).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Muniz et al, 2017
Local modification of chromatin and RNA Pol II speed was exemplified in cells undergoing oncogene-induced senescence downstream of two genes, leading to extended transcriptional read-through.
“We recently exemplified such a local modification of chromatin and RNA Pol II speed in cells undergoing oncogene‐induced senescence downstream of two genes, leading to extended transcriptional read‐through (Muniz et al, 2017).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Muniz et al, 2017
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Additional file 1 of ARTDeco: automatic readthrough transcription detection
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Additional file 2 of Intergenic RNA mainly derives from nascent transcripts of known genes
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Additional file 1 of Intergenic RNA mainly derives from nascent transcripts of known genes
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Abdi-Galab, M. (2023) · theses.fr (ABES) · doi:10.70675/d647d7abzc285z4aadza80az4d9bb3925e9e
BDNF-DT and BDNF-AS-DT: novel genes in the BDNF locus
Bach, S. V., Punzi, G., Smith, N. E., Mukherjee, S., Shin, J. H., Chen, Q., Pertea, G. M., Collado‐Torres, L., Maynard, K. R., Page, S. C., et al. (2026) · Molecular Psychiatry · doi:10.1038/s41380-026-03695-0
- Authors
- Muniz, L., Deb, M. K., Aguirrebengoa, M., Lazorthes, S., Trouche, D., & Nicolas, E.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Nicolas, Estelle
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2017-11
- Volume
- 21
- Issue
- 9
- Pages
- 2433-2446
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2768145059
- Cited by
- 56
- References
- 35
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 7 · 2023: 6 · 2022: 7 · 2021: 13 · 2020: 10 · 2019: 2 · 2018: 4 · 2017: 1
- FWCI
- 1.90
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- La Ligue Nationale contre le Cancer
- Fondation ARC (Association pour la Recherche sur le Cancer)
- French Ministry of Science
- Ligue Nationale Contre le Cancer
- Fondation ARC
- FRM (Fondation pour la Recherche Médicale)
- ANR (Agence Nationale de la Recherche, Pings program)
- INCa (Institut National du Cancer, PLBIO 2012 (DA No. 2012-123)
- Fondation ARC (Progamme ARC (PGA120150202320)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- cellular senescence, antisense RNA, read-through transcription, RNA polymerase II elongation, transcription termination, histone H2A.Z, chromatin regulation, intergenic regions, gene expression inhibition
- MeSH terms
- Cell Line, Chromatin, Gene Expression Regulation, Humans, Promoter Regions, Genetic, RNA Polymerase II, Transcription, Genetic, RNA, Antisense, Cellular Senescence, Computational Biology
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