Translation and replication of hepatitis C virus genomic RNA depends on ancient cellular proteins that control mRNA fates.
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.
Scheller
Nicoletta
N
Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain.
Mina
Leonardo Bruno
LB
Galão
Rui Pedro
RP
Chari
Ashwin
A
Giménez-Barcons
Mireia
M
Noueiry
Amine
A
Fischer
Utz
U
Meyerhans
Andreas
A
Díez
Juana
J
D020413:3' Untranslated Regions / Q000378:metabolism; D020121:5' Untranslated Regions / Q000235:genetics; D045744:Cell Line, Tumor; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004722:Endoribonucleases / Q000378:metabolism; D005095:Exoribonucleases / Q000378:metabolism; D020868:Gene Silencing; D016679:Genome, Viral / Q000235:genetics*; D016174:Hepacivirus / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000378:metabolism; D012093:Replicon / Q000235:genetics; D015398:Signal Transduction; D014779:Virus Replication
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D004268:DNA-Binding Proteins; C464824:LSM1 protein, human; D008869:Microtubule-Associated Proteins; C526510:PATL1 protein, human; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D004722:Endoribonucleases; D005095:Exoribonucleases; C470512:XRN1 protein, human; C467723:DCP2 protein, human; C094683:DDX6 protein, human; D053487:DEAD-box RNA Helicases