Translation of hepatitis C virus genome.

Abstract

Translation of the human hepatitis C virus (HCV) RNA genome occurs by internal ribosome entry through the 5' end (5' noncoding region) in a cap-independent fashion. The relatively long stretch of this noncoding region contains multiple initiation codons that are apparently not used for translation. Translation of the HCV polyprotein is initiated instead from an AUG located at nt 342. Using computer-assisted analysis (and subsequently substantiated by enzymatic probing), a complex secondary and tertiary structure of the 5' noncoding region (5'NCR) has been predicted. Based on an RNA folding model proposed by Brown et al. (1992), a detailed mutational analysis carried out identified the key secondary structural regions that are of functional significance in translational control. Maintenance of a helical structural element relevant to an oligopyrimidine tract is essential for internal initiation. A putative coaxial stacking or a pseudoknot structure upstream of the initiator AUG seems to be central to an internal ribosome entry site (IRES)-mediated translation of the HCV RNA genome.