dichtl-cordycepin-2009.pdf (1.85 MB)
Cordycepin interferes with 3' end formation in yeast independently of its potential to terminate RNA chain elongation
journal contribution
posted on 2009-03-26, 00:00 authored by S Holbein, A Wengi, L Decourty, F Freimoser, A Jacquier, Bernhard DichtlBernhard DichtlCordycepin (3′ deoxyadenosine) is a biologically active compound that, when incorporated during RNA synthesis in vitro, provokes chain termination due to the absence of a 3′ hydroxyl moiety. We were interested in the effects mediated by this drug in vivo and analyzed its impact on RNA metabolism of yeast. Our results support the view that cordycepin-triphosphate (CoTP) is the toxic component that is limiting cell growth through inhibition of RNA synthesis. Unexpectedly, cordycepin treatment modulated 3′ end heterogeneity of ACT1 and ASC1 mRNAs and rapidly induced extended transcripts derived from CYH2 and NEL025c loci. Moreover, cordycepin ameliorated the growth defects of poly(A) polymerase mutants and the pap1-1 mutation neutralized the effects of the drug on gene expression. Our observations are consistent with an epistatic relationship between poly(A) polymerase function and cordycepin action and suggest that a major mode of cordycepin activity reduces 3′ end formation efficiency independently of its potential to terminate RNA chain elongation. Finally, chemical-genetic profiling revealed genome-wide pathways linked to cordycepin activity and identified novel genes involved in poly(A) homeostasis.
History
Journal
RNAVolume
15Issue
5Pagination
837 - 849Publisher
Cold Spring Harbor Laboratory PressLocation
Woodbury, N.Y.Publisher DOI
Link to full text
ISSN
1355-8382eISSN
1469-9001Language
engPublication classification
C1.1 Refereed article in a scholarly journalCopyright notice
2009, Cold Spring Harbor Laboratory PressUsage metrics
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cordycepinSaccharomyces cerevisiaeRNAtranscription39 end formationpoly(A)ATPScience & TechnologyLife Sciences & BiomedicineBiochemistry & Molecular Biology3 ' end formationPOLYMERASE-II TRANSCRIPTIONCRYPTIC UNSTABLE TRANSCRIPTSMESSENGER-RNASACCHAROMYCES-CEREVISIAEPOLY(A) POLYMERASEIN-VIVOSCIENTIFIC REDISCOVERY3'-END FORMATIONQUALITY CONTROLGENE
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