The hepatitis C virus 3′-untranslated region or a poly(A) tract promote efficient translation subsequent to the initiation phase

• Published in: Nucleic acids research 2006-01, Vol.34 (4), p.1293-1303
• Main Authors: Bradrick, Shelton S., Walters, Robert W., Gromeier, Matthias
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions; 5' Untranslated Regions; Base Sequence; Cell Line, Tumor; Gene Expression Regulation, Viral; Hepacivirus - genetics; Humans; Molecular Sequence Data; Peptide Chain Initiation, Translational; Peptide Chain Termination, Translational; Protein Biosynthesis; Regulatory Sequences, Ribonucleic Acid; RNA 3' Polyadenylation Signals; RNA Stability; RNA, Viral - chemistry
• ISSN: 0305-1048; 1362-4962
• DOI: 10.1093/nar/gkl019

Enhancement of eukaryotic messenger RNA (mRNA) translation initiation by the 3′ poly(A) tail is mediated through interaction of poly(A)-binding protein with eukaryotic initiation factor (eIF) 4G, bridging the 5′ terminal cap structure. In contrast to cellular mRNA, translation of the uncapped, non-polyadenylated hepatitis C virus (HCV) genome occurs independently of eIF4G and a role for 3′-untranslated sequences in modifying HCV gene expression is controversial. Utilizing cell-based and in vitro translation assays, we show that the HCV 3′-untranslated region (UTR) or a 3′ poly(A) tract of sufficient length interchangeably stimulate translation dependent upon the HCV internal ribosomal entry site (IRES). However, in contrast to cap-dependent translation, the rate of initiation at the HCV IRES was unaffected by 3′-untranslated sequences. Analysis of post-initiation events revealed that the 3′ poly(A) tract and HCV 3′-UTR improve translation efficiency by enabling termination and possibly ribosome recycling for successive rounds of translation.