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Bimodal expression of PHO84 is modulated by early termination of antisense transcription

Rahman, Samir
Zenklusen, Daniel
Published in Nature structural & molecular biology. 2013, vol. 20, no. 7, p. 851-858
Abstract Many Saccharomyces cerevisiae genes encode antisense transcripts, some of which are unstable and degraded by the exosome component Rrp6. Loss of Rrp6 results in the accumulation of long PHO84 antisense (AS) RNAs and repression of sense transcription through PHO84 promoter deacetylation. We used single-molecule resolution fluorescent in situ hybridization (smFISH) to investigate antisense-mediated transcription regulation. We show that PHO84 AS RNA acts as a bimodal switch, in which continuous, low-frequency antisense transcription represses sense expression within individual cells. Surprisingly, antisense RNAs do not accumulate at the PHO84 gene but are exported to the cytoplasm. Furthermore, rather than stabilizing PHO84 AS RNA, the loss of Rrp6 favors its elongation by reducing early transcription termination by Nrd1-Nab3-Sen1. These observations suggest that PHO84 silencing results from antisense transcription through the promoter rather than the static accumulation of antisense RNAs at the repressed gene.
Keywords DNA Helicases/physiologyExosome Multienzyme Ribonuclease Complex/physiologyGene Expression Regulation, FungalHistone Deacetylases/physiologyHistone-Lysine N-Methyltransferase/physiologyIn Situ Hybridization, FluorescenceMetalloendopeptidases/physiologyModels, GeneticMultiprotein ComplexesNuclear Proteins/physiologyPolyadenylationPolynucleotide Adenylyltransferase/physiologyPromoter Regions, Genetic/geneticsProton-Phosphate Symporters/biosynthesis/geneticsRNA Helicases/physiologyRNA, Antisense/genetics/metabolismRNA, Fungal/genetics/metabolismRNA, Messenger/biosynthesis/metabolismRNA-Binding Proteins/physiologySaccharomyces cerevisiae/geneticsSaccharomyces cerevisiae Proteins/biosynthesis/genetics/physiologyTranscription, Genetic
PMID: 23770821
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Article (Published version) (2.3 MB) - public document Free access
Research group Groupe Stutz
Swiss National Science Foundation: 31003A_130292
(ISO format)
CASTELNUOVO, Manuele et al. Bimodal expression of PHO84 is modulated by early termination of antisense transcription. In: Nature structural & molecular biology, 2013, vol. 20, n° 7, p. 851-858. doi: 10.1038/nsmb.2598 https://archive-ouverte.unige.ch/unige:36376

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Deposited on : 2014-05-06

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