title: HCV IRES interacts with the 18S rRNA to activate the 40S ribosome for subsequent steps of translation initiation.
abstract: Previous analyses of complexes of 40S ribosomal subunits with the hepatitis C virus (HCV) internal ribosome entry site (IRES) have revealed contacts made by the IRES with ribosomal proteins. Here, using chemical probing, we show that the HCV IRES also contacts the backbone and bases of the CCC triplet in the 18S ribosomal RNA (rRNA) expansion segment 7. These contacts presumably provide interplay between IRES domain II and the AUG codon close to ribosomal protein S5, which causes a rearrangement of 18S rRNA structure in the vicinity of the universally conserved nucleotide G1639. As a result, G1639 becomes exposed and the corresponding site of the 40S subunit implicated in transfer RNA discrimination can select . These data are the first demonstration at nucleotide resolution of direct IRES-rRNA interactions and how they induce conformational transition in the 40S subunit allowing the HCV IRES to function without AUG recognition initiation factors.
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, Russia and Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119991, Russia.
authors.forename: Alexey A
authors.initials: AA
authors.lastname: Malygin
authors.forename: Olga A
authors.initials: OA
authors.lastname: Kossinova
authors.forename: Ivan N
authors.initials: IN
authors.lastname: Shatsky
authors.forename: Galina G
authors.initials: GG
authors.lastname: Karpova
mesh_terms: D020121:5' Untranslated Regions; D001483:Base Sequence; D003062:Codon; D016174:Hepacivirus / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D010442:Peptide Chain Initiation, Translational; D012333:RNA, Messenger / Q000378:metabolism; D012337:RNA, Ribosomal, 18S / Q000737:chemistry / Q000378:metabolism*; D012367:RNA, Viral / Q000737:chemistry*; D054682:Ribosome Subunits, Small, Eukaryotic / Q000378:metabolism*
chemical_list: D020121:5' Untranslated Regions; D003062:Codon; D012333:RNA, Messenger; D012337:RNA, Ribosomal, 18S; D012367:RNA, Viral