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Muniz, Lisa; Deb, Maharshi Krishna; Aguirrebengoa, Marion; Lazorthes, Sandra; Trouche, Didier; Nicolas, Estelle
Cell reports (Cambridge), 11/2017, Letnik: 21, Številka: 9Journal Article
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. Display omitted •START RNAs are produced by transcriptional read-through at convergent genes•In senescence, they repress the expression of the genes to which they are antisense•RNA pol II elongation rate is regulated downstream of convergent genes at START loci•H2A.Z histone variant represses START RNAs in proliferative cells Muniz et al. identified a family of functional antisense RNAs produced by transcriptional read-through downstream of convergent genes. These RNAs are activated during senescence by mechanisms relying on the control of RNA pol II elongation rate and H2A.Z local occupancy, emphasizing the importance of controlling chromatin structure at intergenic regions.
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