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. 2004 Oct 29;119(3):369-80.
doi: 10.1016/j.cell.2004.09.038.

The pathway of HCV IRES-mediated translation initiation

Geoff A Otto  1 , Joseph D Puglisi
Affiliations
Free article

The pathway of HCV IRES-mediated translation initiation

Geoff A Otto et al. Cell. .
Free article

Abstract

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.

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