ObjectivesTo determine the role of the hepatitis C virus 3´ untranslated region in viral mRNA translation in transfected cells and in cell extracts.Study Design/MethodsNoninfectious hepatitis C virus mini-genome RNAs with various deletions in the viral 3´ untranslated region were transfected into cells or translated in vitro, and the translation efficiency was determined.ResultsWe have found that the presence of the hepatitis C virus 3´ untranslated region modestly increases mRNA translation. The positive effect correlated with the binding of a 45-kDa cytoplasmic factor to the hepatitis C virus 3´ untranslated region. Furthermore, the U-rich sequence in the hepatitis C virus 3´ untranslated region inhibits translation of capped and polyadenylated mRNAs as a result of the hybridization.ConclusionsThe modest effect of the hepatitis C virus 3´ untranslated region on translation suggests that it does not play a major role in mRNA translation. The inhibitory effect of the hepatitis C virus 3´ untranslated region on translation of polyadenylated mRNAs supports the notion that translation of hepatitis C virus mRNAs occurs independently of a polyA tail.