The hepatitis C virus 3'-untranslated region or a poly(A) tract promote efficient translation subsequent to the initiation phase.
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.
Bradrick
Shelton S
SS
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
Walters
Robert W
RW
Gromeier
Matthias
M
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D001483:Base Sequence; D045744:Cell Line, Tumor; D015967:Gene Expression Regulation, Viral; D016174:Hepacivirus / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D010442:Peptide Chain Initiation, Translational; D010443:Peptide Chain Termination, Translational; D014176:Protein Biosynthesis; D039104:RNA 3' Polyadenylation Signals; D020871:RNA Stability; D012367:RNA, Viral / Q000737:chemistry*; D038621:Regulatory Sequences, Ribonucleic Acid
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D012367:RNA, Viral; D038621:Regulatory Sequences, Ribonucleic Acid