Antisense transcriptional interference mediates tight gene repression in budding yeast

Pervasive transcription generates mainly unstable non-coding transcripts. Although a few examples of pervasive antisense have been shown to mediate gene regulation by transcriptional interference, whether pervasive transcription has a general functional role or merely represents transcriptional noise remains to be determined. In a mutant context that revealed pervasive transcripts, we characterized more than 800 antisenses genome wide and analysed the corresponding sense mRNA behaviour. We observed that antisense non-coding transcription is commonly found associated with genes tightly repressed during the exponential phase with an opposite level of mRNA and the associated antisense. This suggested that antisense transcription might participate to a tight repression of genes during the exponential phase. We thus specifically interrupted the antisense transcription of a subset of genes, and found that it resulted in a de-repression of the corresponding mRNAs. We further validated that this repression acts in cis through a transcriptional interference mechanism, which involves several chromatin modification factors. Transcription interference is observed for the first time as a general mean of gene regulation between cellular states. Overall design: mRNA and 3''RACE of yeast WT and UPF1? in stationary and quiescent phase.

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Nevers A, Doyen A, Malabat C, Néron B, Kergrohen T, Jacquier A, Badis G