Journal
NATURE STRUCTURAL & MOLECULAR BIOLOGY
Volume 20, Issue 7, Pages 851-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.2598
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Funding
- SystemsX
- Novartis
- EMBO
- Swiss National Science Foundation [31003A_130292]
- National Center of Competence in Research Frontiers in Genetics, IGE3
- Canton of Geneva
- Canadian Institutes of Health Research [MOP-BMB-232642]
- Canadian Foundation for Innovation
- Fonds de recherche du Quebec-Sante
- Swiss National Science Foundation (SNF) [31003A_130292] Funding Source: Swiss National Science Foundation (SNF)
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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.
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