Switch from translation to RNA replication in a positive-stranded RNA virus.
In positive-stranded viruses, the genomic RNA serves as a template for both translation and RNA replication. Using poliovirus as a model, we examined the interaction between these two processes. We show that the RNA polymerase is unable to replicate RNA templates undergoing translation. We discovered that an RNA structure at the 5' end of the viral genome, next to the internal ribosomal entry site, carries signals that control both viral translation and RNA synthesis. The interaction of this RNA structure with the cellular factor PCBP up-regulates viral translation, while the binding of the viral protein 3CD represses translation and promotes negative-strand RNA synthesis. We propose that the interaction of 3CD with this RNA structure controls whether the genomic RNA is used for translation or RNA replication.
Gamarnik
A V
AV
Department of Microbiology and Immunology, University of California, San Francisco, California 94143-0414 USA.
Andino
R
R
D000086042:3C Viral Proteases; D000818:Animals; D001483:Base Sequence; D002451:Cell Compartmentation; D003546:Cysteine Endopeptidases / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D005260:Female; D016679:Genome, Viral; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009865:Oocytes / Q000378:metabolism; D017955:Poliovirus / Q000235:genetics* / Q000378:metabolism*; D014176:Protein Biosynthesis; D012367:RNA, Viral / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D012324:RNA-Dependent RNA Polymerase; D012270:Ribosomes / Q000378:metabolism; D014764:Viral Proteins; D014981:Xenopus
D012367:RNA, Viral; D014764:Viral Proteins; C090443:polymerase 3Dpol, poliovirus; D012324:RNA-Dependent RNA Polymerase; D012321:DNA-Directed RNA Polymerases; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases