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

Turner, Rachael Emily, Harrison, Paul F, Swaminathan, Angavai, Kraupner-Taylor, Calvin A, Goldie, Belinda J, See, Michael, Peterson, Amanda L, Schittenhelm, Ralf B, Powell, David R, Creek, Darren J, Dichtl, Bernhard and Beilharz, Traude H 2021, Genetic and pharmacological evidence for kinetic competition between alternative poly(A) sites in yeast, eLife, vol. 10, pp. 1-35, doi: 10.7554/elife.65331.

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Title Genetic and pharmacological evidence for kinetic competition between alternative poly(A) sites in yeast
Author(s) Turner, Rachael Emily
Harrison, Paul F
Swaminathan, Angavai
Kraupner-Taylor, Calvin A
Goldie, Belinda J
See, Michael
Peterson, Amanda L
Schittenhelm, Ralf B
Powell, David R
Creek, Darren J
Dichtl, BernhardORCID iD for Dichtl, Bernhard orcid.org/0000-0001-5514-4982
Beilharz, Traude H
Journal name eLife
Volume number 10
Article ID e65331
Start page 1
End page 35
Total pages 35
Publisher eLife Sciences Publications, Ltd
Place of publication Cambridge, Eng.
Publication date 2021
ISSN 2050-084X
2050-084X
Keyword(s) alternative polyadenylation
chromosomes
cleavage
cordycepin
gene expression
genetics
genomics
mycophenolic acid
polyadenylation
S. cerevisiae
Sen1
transcription elongation
Summary 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 rpb1 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.
Language eng
DOI 10.7554/elife.65331
Indigenous content off
Field of Research 0601 Biochemistry and Cell Biology
HERDC Research category C1 Refereed article in a scholarly journal
Free to Read? Yes
Persistent URL http://hdl.handle.net/10536/DRO/DU:30153600

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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.