Cordycepin interferes with 3' end formation in yeast independently of its potential to terminate RNA chain elongation
| Autor: | Bernhard Dichtl, Agnieszka Wengi, Sandra Holbein, Laurence Decourty, Florian M. Freimoser, Alain Jacquier |
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| Přispěvatelé: | University of Zurich, Dichtl, B |
| Rok vydání: | 2009 |
| Předmět: |
DNA polymerase
Gene Expression Pancreatitis-Associated Proteins Saccharomyces cerevisiae Article chemistry.chemical_compound Deoxyadenosine Transcription (biology) Gene expression 1312 Molecular Biology RNA Messenger Molecular Biology Polymerase biology Cordycepin Deoxyadenosines RNA Polynucleotide Adenylyltransferase RNA Fungal 10124 Institute of Molecular Life Sciences Biochemistry chemistry Polynucleotide adenylyltransferase biology.protein 570 Life sciences Genome Fungal |
| Zdroj: | RNA (New York, N.Y.). 15(5) |
| ISSN: | 1469-9001 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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