Translation and replication of hepatitis C virus genomic RNA depends on ancient cellular proteins that control mRNA fates

Nicoletta Scheller; Leonardo Bruno Mina; Rui Pedro Galão; Ashwin Chari; Mireia Giménez-Barcons; Amine Noueiry; Utz Fischer; Andreas Meyerhans; Juana Díez

doi:10.1073/pnas.0906413106

Translation and replication of hepatitis C virus genomic RNA depends on ancient cellular proteins that control mRNA fates

Proc Natl Acad Sci U S A. 2009 Aug 11;106(32):13517-22. doi: 10.1073/pnas.0906413106. Epub 2009 Jul 23.

Authors

Nicoletta Scheller¹, Leonardo Bruno Mina, Rui Pedro Galão, Ashwin Chari, Mireia Giménez-Barcons, Amine Noueiry, Utz Fischer, Andreas Meyerhans, Juana Díez

Affiliation

¹ Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3' Untranslated Regions / metabolism
5' Untranslated Regions / genetics
Cell Line, Tumor
DEAD-box RNA Helicases / metabolism
DNA-Binding Proteins / metabolism
Endoribonucleases / metabolism
Exoribonucleases / metabolism
Gene Silencing
Genome, Viral / genetics*
Hepacivirus / genetics*
Hepacivirus / pathogenicity
Hepacivirus / physiology*
Humans
Microtubule-Associated Proteins / metabolism
Nucleic Acid Conformation
Protein Binding
Protein Biosynthesis*
Proteins / metabolism*
Proto-Oncogene Proteins / metabolism
RNA, Messenger / genetics
RNA, Messenger / metabolism
RNA, Viral / chemistry
RNA, Viral / genetics*
RNA-Binding Proteins / metabolism
Replicon / genetics
Signal Transduction
Virus Replication*

Substances

3' Untranslated Regions
5' Untranslated Regions
DNA-Binding Proteins
LSM1 protein, human
Microtubule-Associated Proteins
PATL1 protein, human
Proteins
Proto-Oncogene Proteins
RNA, Messenger
RNA, Viral
RNA-Binding Proteins
Endoribonucleases
Exoribonucleases
XRN1 protein, human
DCP2 protein, human
DDX6 protein, human
DEAD-box RNA Helicases