Translation and replication of hepatitis C virus genomic RNA depends on ancient cellular proteins that control mRNA fates
- Nicoletta Schellera,b,1,
- Leonardo Bruno Minaa,1,
- Rui Pedro Galãoa,1,
- Ashwin Charic,
- Mireia Giménez-Barconsa,
- Amine Noueiryd,2,
- Utz Fischerc,
- Andreas Meyerhansb and
- Juana Díeza,3
- aDepartment of Experimental and Health Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain;
- bInstitute of Virology, Saarland University, D-66421 Homburg, Germany;
- cDepartment of Biochemistry, Biocenter, University of Wuerzburg, Am Hubland, D-97074 Wuerzburg, Germany; and
- dApath, LLC, St. Louis, MO 63110
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↵2Present address: Polsinelli, St. Louis, MO 63102.
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Communicated by Paul Ahlquist, University of Wisconsin, Madison, WI, June 15, 2009
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↵1N.S., L.B.M., and R.P.G. contributed equally to this work. (received for review September 11, 2008)
Abstract
Inevitably, viruses depend on host factors for their multiplication. Here, we show that hepatitis C virus (HCV) RNA translation and replication depends on Rck/p54, LSm1, and PatL1, which regulate the fate of cellular mRNAs from translation to degradation in the 5′-3′-deadenylation-dependent mRNA decay pathway. The requirement of these proteins for efficient HCV RNA translation was linked to the 5′ and 3′ untranslated regions (UTRs) of the viral genome. Furthermore, LSm1–7 complexes specifically interacted with essential cis-acting HCV RNA elements located in the UTRs. These results bridge HCV life cycle requirements and highly conserved host proteins of cellular mRNA decay. The previously described role of these proteins in the replication of 2 other positive-strand RNA viruses, the plant brome mosaic virus and the bacteriophage Qß, pinpoint a weak spot that may be exploited to generate broad-spectrum antiviral drugs.
Footnotes
- 3To whom correspondence should be addressed at: Universitat Pompeu Fabra, Department of Experimental and Health Sciences, Dr. Aiguader 88, 08003, Barcelona, Spain. E-mail: juana.diez{at}upf.edu
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Author contributions: A.N., U.F., A.M., and J.D. designed research; N.S., L.B.M., R.P.G., A.C., and M.G.-B. performed research; and A.M. and J.D. wrote the paper.
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The authors declare no conflict of interest.
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This article contains supporting information online at www.pnas.org/cgi/content/full/0906413106/DCSupplemental.
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Freely available online through the PNAS open access option.
