Author:
Yague-Sanz Carlo,Vanrobaeys Yann,Fernandez Ronan,Duval Maxime,Larochelle Marc,Beaudoin Jude,Berro Julien,Labbé Simon,Jacques Pierre-Étienne,Bachand François
Abstract
Transcription by RNA polymerase II (RNAPII) is a dynamic process with frequent variations in the elongation rate. However, the physiological relevance of variations in RNAPII elongation kinetics has remained unclear. Here we show in yeast that a RNAPII mutant that reduces the transcription elongation rate causes widespread changes in alternative polyadenylation (APA). We unveil two mechanisms by which APA affects gene expression in the slow mutant: 3′ UTR shortening and gene derepression by premature transcription termination of upstream interfering noncoding RNAs. Strikingly, the genes affected by these mechanisms are enriched for functions involved in phosphate uptake and purine synthesis, processes essential for maintenance of the intracellular nucleotide pool. As nucleotide concentration regulates transcription elongation, our findings argue that RNAPII is a sensor of nucleotide availability and that genes important for nucleotide pool maintenance have adopted regulatory mechanisms responsive to reduced rates of transcription elongation.
Funder
Natural Sciences and Engineering Research Council of Canada
National Institutes of Health
National Institute of General Medical Sciences
Fonds de recherche du Québec-Santé
Publisher
Cold Spring Harbor Laboratory
Subject
Developmental Biology,Genetics
Cited by
32 articles.
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