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

Carlo Yague-Sanz, Yann Vanrobaeys, Ronan Fernandez, Maxime Duval, Marc Larochelle, Jude Beaudoin, Julien Berro, Simon Labbé, Pierre Étienne Jacques, François Bachand

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1-15
Number of pages15
JournalGenes and Development
Volume34
Issue number13-14
DOIs
Publication statusPublished - Jul 2020
Externally publishedYes

Keywords

  • Alternative polyadenylation
  • NTP sensing
  • Phosphate starvation
  • RNA polymerase II
  • Transcription elongation rate
  • Transcription termination

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