title: The hepatitis C virus RNA 3'-untranslated region strongly enhances translation directed by the internal ribosome entry site.
abstract: The positive-strand RNA genome of the hepatitis C virus (HCV) is flanked by 5'- and 3'-untranslated regions (UTRs). Translation of the viral RNA is directed by the internal ribosome entry site (IRES) in the 5'-UTR, and subsequent viral RNA replication requires sequences in the 3'-UTR and in the 5'-UTR. Addressing previous conflicting reports on a possible function of the 3'-UTR for RNA translation in this study, we found that reporter construct design is an important parameter in experiments testing 3'-UTR function. A translation enhancer function of the HCV 3'-UTR was detected only after transfection of monocistronic reporter RNAs or complete RNA genomes having a 3'-UTR with a precise 3' terminus. The 3'-UTR strongly stimulates HCV IRES-dependent translation in human hepatoma cell lines but only weakly in nonliver cell lines. The variable region, the poly(U . C) tract, and the most 3' terminal stem-loop 1 of the highly conserved 3' X region contribute significantly to translation enhancement, whereas stem-loops 2 and 3 of the 3' X region are involved only to a minor extent. Thus, the signals for translation enhancement and for the initiation of RNA minus-strand synthesis in the HCV 3'-UTR partially overlap, supporting the idea that these sequences along with viral and possibly also cellular factors may be involved in an RNA 3'-5' end interaction and a switch between translation and RNA replication.
authors.affiliation: Institute of Biochemistry, Faculty of Medicine, Justus-Liebig-University Giessen, Friedrichstrasse 24, 35392 Giessen, Germany.
authors.forename: Yutong
authors.initials: Y
authors.lastname: Song
authors.forename: Peter
authors.initials: P
authors.lastname: Friebe
authors.forename: Eleni
authors.initials: E
authors.lastname: Tzima
authors.forename: Christiane
authors.initials: C
authors.lastname: Jünemann
authors.forename: Ralf
authors.initials: R
authors.lastname: Bartenschlager
authors.forename: Michael
authors.initials: M
authors.lastname: Niepmann
mesh_terms: D020413:3' Untranslated Regions / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D002460:Cell Line; D016174:Hepacivirus / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology / Q000821:virology; D014176:Protein Biosynthesis / Q000187:drug effects*; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics*; D012270:Ribosomes / Q000378:metabolism / Q000821:virology; D014779:Virus Replication / Q000187:drug effects* / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D012367:RNA, Viral