title: Translational enhancement of HCV RNA genotype 1b by 3'-untranslated and envelope 2 protein-coding sequences.
abstract: HCV RNA has a unique regulatory mechanism for translation. The X region of 3'-UTR and core-coding sequence regulate HCV translation. In this study, we clarified that the entire 3'-UTR also enhances HCV translation, and the envelope-coding sequence of HCV genotype 1b increases degree of this enhancement. In the luciferase reporter assay using rabbit reticulocyte lysates, translational enhancement by 3'-UTR with core to E2 regions was 25-fold higher when compared with control RNA lacking the 3'-UTR. Presence of the entire E2 sequence was important for this enhancement. This phenomenon was not due to transcript stability, and envelope protein alone did not affect translation. E2-coding sequence of genotype 1a had no effect on translation. We observed the same results in animal cell culture systems using bicistronic RNA. Structural protein-coding sequences and 3'-UTR of HCV RNA regulate viral translation, and a target for antiviral agents may be present in these regions.
authors.affiliation: The Second Department of Internal Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Morikawa
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Ito
authors.forename: Hisako
authors.initials: H
authors.lastname: Nozawa
authors.forename: Momoko
authors.initials: M
authors.lastname: Inokuchi
authors.forename: Manabu
authors.initials: M
authors.lastname: Uchikoshi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Saito
authors.forename: Keiji
authors.initials: K
authors.lastname: Mitamura
authors.forename: Michio
authors.initials: M
authors.lastname: Imawari
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D012156:Reticulocytes; D012270:Ribosomes / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D012367:RNA, Viral; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus