TY - JOUR
T1 - Nutrient-dependent control of RNA polymerase II elongation rate regulates specific gene expression programs by alternative polyadenylation
AU - Yague-Sanz, Carlo
AU - Vanrobaeys, Yann
AU - Fernandez, Ronan
AU - Duval, Maxime
AU - Larochelle, Marc
AU - Beaudoin, Jude
AU - Berro, Julien
AU - Labbé, Simon
AU - Jacques, Pierre Étienne
AU - Bachand, François
N1 - Funding Information:
We thank Beate Schwer, Damien Hermand, and Francois Robert for critical reading of the manuscript, and the sequencing platforms of the McGill University and Génome Québec Innovation Centre; Calcul Québec and Compute Canada provided the computing infrastructure used to analyze the data. This work was supported by funding from the Natural Sciences and Engineering Research Council of Canada (NSERC) to F.B. (RGPIN-2017- 05482). J. Berro and R.F. are supported by National Institutes of Health/National Institute of General Medical Sciences grant R01GM115636. P.-É.J. and C.Y.S. are supported by the Fonds de recherche du Québec-Santé (FRQS). F.B. holds a Canada Research Chair in Quality Control of Gene Expression.
Funding Information:
We thank Beate Schwer, Damien Hermand, and Francois Robert for critical reading of the manuscript, and the sequencing platforms of the McGill University and Génome Québec Innovation Centre; Calcul Québec and Compute Canada provided the computing infrastructure used to analyze the data. This work was supported by funding from the Natural Sciences and Engineering Research Council of Canada (NSERC) to F.B. (RGPIN-2017-05482). J. Berro and R.F. are supported by National Institutes of Health/National Institute of General Medical Sciences grant R01GM115636. P.-É.J. and C.Y.S. are supported by the Fonds de recherche du Québec-Santé (FRQS). F.B. holds a Canada Research Chair in Quality Control of Gene Expression.
Publisher Copyright:
© 2020 Yague-Sanz et al.
PY - 2020/7
Y1 - 2020/7
N2 - 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.
AB - 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.
KW - Alternative polyadenylation
KW - NTP sensing
KW - Phosphate starvation
KW - RNA polymerase II
KW - Transcription elongation rate
KW - Transcription termination
UR - http://www.scopus.com/inward/record.url?scp=85087532389&partnerID=8YFLogxK
U2 - 10.1101/GAD.337212.120
DO - 10.1101/GAD.337212.120
M3 - Article
C2 - 32499400
AN - SCOPUS:85087532389
SN - 0890-9369
VL - 34
SP - 883
EP - 897
JO - Genes and Development
JF - Genes and Development
IS - 13-14
ER -