Genetic screen for suppression of transcriptional interference identifies a gain-of-function mutation in Pol2 termination factor Seb1
Beate Schwer, Angad Garg, Agata Jacewicz, Stewart Shuman
Abstract
Significance Long noncoding RNA (lncRNA) transcriptional interference with the synthesis of downstream messenger RNAs underlies regulated biological responses of yeast cells to nutrient availability. For example, expression of the phosphate ( PHO ) regulon in phosphate-replete fission yeast cells is tunable by genetic manipulations that favor or disfavor precocious lncRNA 3′-processing/termination. A forward genetic screen for relief of lncRNA interference with pho1 expression uncovered a mutation G476S in the RNA-binding domain of essential termination factor Seb1 that evokes precocious lncRNA termination in response to 5′-proximal poly(A) sites in a manner dependent on cleavage and polyadenylation factor CPF, termination factor Rhn1, and inositol pyrophosphate synthesis. Multiple lines of evidence point to Seb1-G476S as a unique gain-of-function mutation in a Pol2 transcription termination factor.