Translation of hepatitis C virus RNA

The 341-nucleotide 5' non-translated region is the most conserved part of t he hepatitis C virus (HCV) genome, It contains a highly structured internal ribosomal entry site (IRES) that mediates cap-independent initiation of tr anslation of the viral polyprotein by a mechanism that is unprecedented in eukaryotes. The first step in translation initiation is assembly of eukaryo tic initiation factor (eIF) 3, eIF2, GTP, initiator tRNA and a 40S ribosoma l subunit into a 43S preinitiation complex, The HCV IRES recruits this comp lex and directs its precise attachment at the initiation codon to form a 48 S complex in a process that does not involve eIFs 4A, 4B or 4F. The IRES co ntains sites that bind independently with the eIF3 and 40S subunit componen ts of 43S complexes, and structural determinants that ensure the correct sp atial orientation of these binding sites so that the 48S complex assembles precisely at the initiation codon.