Nutrient-dependent control of RNA polymerase II elongation rate regulates specific gene expression programs by alternative polyadenylation

  1. François Bachand1
  1. 1Department of Biochemistry and Functional Genomics, Université de Sherbrooke, Sherbrooke, Québec J1E 4K8, Canada;
  2. 2Department of Molecular Biophysics and Biochemistry, Yale School of Medicine, New Haven, Connecticut 06520, USA;
  3. 3Department of Cell Biology, Yale School of Medicine, New Haven, Connecticut 06520, USA;
  4. 4Department of Biology, Université de Sherbrooke, Sherbrooke, Québec J1K 2R1, Canada
  1. Corresponding author: f.bachand{at}usherbrooke.ca
  1. 6 These authors contributed equally to this work.

  • 5 Present address: Interdisciplinary Graduate Program in Genetics, University of Iowa, Iowa City, IA 52242, USA.

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.

Keywords

Footnotes

  • Supplemental material is available for this article.

  • Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.337212.120.

  • Freely available online through the Genes & Development Open Access option.

  • Received January 28, 2020.
  • Accepted May 6, 2020.

This article, published in Genes & Development, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.

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