Genetic and Pharmacological Evidence for Kinetic Competition Between Alternative Poly(A) Sites in Yeast

Overview

Journal Elife

Specialty Biology

Date 2021 Jul 7

PMID 34232857

Citations 2

Authors

Rachael Emily Turner

Paul F Harrison

Angavai Swaminathan

Calvin A Kraupner-Taylor

Belinda J Goldie

Michael See

Amanda L Peterson

Ralf B Schittenhelm

David R Powell

Darren J Creek

Bernhard Dichtl

Traude H Beilharz

Affiliations

Soon will be listed here.

Abstract

Most eukaryotic mRNAs accommodate alternative sites of poly(A) addition in the 3' untranslated region in order to regulate mRNA function. Here, we present a systematic analysis of 3' end formation factors, which revealed 3'UTR lengthening in response to a loss of the core machinery, whereas a loss of the Sen1 helicase resulted in shorter 3'UTRs. We show that the anti-cancer drug cordycepin, 3' deoxyadenosine, caused nucleotide accumulation and the usage of distal poly(A) sites. Mycophenolic acid, a drug which reduces GTP levels and impairs RNA polymerase II (RNAP II) transcription elongation, promoted the usage of proximal sites and reversed the effects of cordycepin on alternative polyadenylation. Moreover, cordycepin-mediated usage of distal sites was associated with a permissive chromatin template and was suppressed in the presence of an mutation, which slows RNAP II elongation rate. We propose that alternative polyadenylation is governed by temporal coordination of RNAP II transcription and 3' end processing and controlled by the availability of 3' end factors, nucleotide levels and chromatin landscape.

Citing Articles

Seeking a Role for Translational Control by Alternative Polyadenylation in .

Turner R, Beilharz T Microorganisms. 2021; 9(9).

PMID: 34576779 PMC: 8464734. DOI: 10.3390/microorganisms9091885.

Genetic and pharmacological evidence for kinetic competition between alternative poly(A) sites in yeast.

Turner R, Harrison P, Swaminathan A, Kraupner-Taylor C, Goldie B, See M Elife. 2021; 10.

PMID: 34232857 PMC: 8263057. DOI: 10.7554/eLife.65331.

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