The pathway of HCV IRES-mediated translation initiation.
The HCV internal ribosome entry site (IRES) directly regulates the assembly of translation initiation complexes on viral mRNA by a sequential pathway that is distinct from canonical eukaryotic initiation. The HCV IRES can form a binary complex with an eIF-free 40S ribosomal subunit. Next, a 48S-like complex assembles at the AUG initiation codon upon association of eIF3 and ternary complex. 80S complex formation is rate limiting and follows the GTP-dependent association of the 60S subunit. Efficient assembly of the 48S-like and 80S complexes on the IRES mRNA is dependent upon maintenance of the highly conserved HCV IRES structure. This revised model of HCV IRES translation initiation provides a context to understand the function of different HCV IRES domains during translation initiation.
Otto
Geoff A
GA
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Puglisi
Joseph D
JD
D001483:Base Sequence; D006367:HeLa Cells; D016174:Hepacivirus / Q000235:genetics* / Q000378:metabolism; D006526:Hepatitis C / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis / Q000502:physiology; D012367:RNA, Viral / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism*; D013395:Sucrose / Q000378:metabolism
D012367:RNA, Viral; D012269:Ribosomal Proteins; D013395:Sucrose