Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-28699
Holbein, S; Wengi, A; Decourty, L; Freimoser, F M; Jacquier, A; Dichtl, B (2009). Cordycepin interferes with 3' end formation in yeast independently of its potential to terminate RNA chain elongation. RNA, 15(5):837-849.
View at publisher
Cordycepin (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.
60 downloads since deposited on 31 Jan 2010
18 downloads since 12 months
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||07 Faculty of Science > Institute of Molecular Life Sciences|
|Dewey Decimal Classification:||570 Life sciences; biology|
|Deposited On:||31 Jan 2010 17:18|
|Last Modified:||28 Nov 2013 01:47|
|Publisher:||Cold Spring Harbor Laboratory Press|
Users (please log in): suggest update or correction for this item
Repository Staff Only: item control page