title: Translation-competent 48S complex formation on HCV IRES requires the RNA-binding protein NSAP1.
abstract: Translation of many cellular and viral mRNAs is directed by internal ribosomal entry sites (IRESs). Several proteins that enhance IRES activity through interactions with IRES elements have been discovered. However, the molecular basis for the IRES-activating function of the IRES-binding proteins remains unknown. Here, we report that NS1-associated protein 1 (NSAP1), which augments several cellular and viral IRES activities, enhances hepatitis C viral (HCV) IRES function by facilitating the formation of translation-competent 48S ribosome-mRNA complex. NSAP1, which is associated with the solvent side of the 40S ribosomal subunit, enhances 80S complex formation through correct positioning of HCV mRNA on the 40S ribosomal subunit. NSAP1 seems to accomplish this positioning function by directly binding to both a specific site in the mRNA downstream of the initiation codon and a 40S ribosomal protein (or proteins).
authors.affiliation: Department of Life Science, Pohang University of Science and Technology, Pohang, Kyungbuk, Republic of Korea.
authors.forename: Sung Mi
authors.initials: SM
authors.lastname: Park
authors.forename: Ki Young
authors.initials: KY
authors.lastname: Paek
authors.forename: Ka Young
authors.initials: KY
authors.lastname: Hong
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Jang
authors.forename: Sungchan
authors.initials: S
authors.lastname: Cho
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Park
authors.forename: Jong Heon
authors.initials: JH
authors.lastname: Kim
authors.forename: Eric
authors.initials: E
authors.lastname: Jan
authors.forename: Sung Key
authors.initials: SK
authors.lastname: Jang
mesh_terms: D020121:5' Untranslated Regions; D006367:HeLa Cells; D016174:Hepacivirus / Q000235:genetics* / Q000378:metabolism; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000378:metabolism*; D006801:Humans; D010442:Peptide Chain Initiation, Translational; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D054682:Ribosome Subunits, Small, Eukaryotic / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism
chemical_list: D020121:5' Untranslated Regions; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D012333:RNA, Messenger; D012367:RNA, Viral