title: microRNAs stimulate translation initiation mediated by HCV-like IRESes.
abstract: MicroRNAs (miRNAs) are small non-coding RNAs that control gene expression by recognizing and hybridizing to a specific sequence generally located in the 3΄ untranslated region (UTR) of targeted mRNAs. miRNA-induced inhibition of translation occurs during the initiation step, most probably at the level of ribosome scanning. In this process, the RNA-induced silencing complex interacts both with PABP and the 43S pre-initiation complex to disrupt scanning of the 40S ribosome. However, in some specific cases, miRNAs can stimulate translation. Although the mechanism of miRNA-mediated upregulation is unknown, it appears that the poly(A) tail and the lack of availability of the TNRC6 proteins are amongst major determinants. The genomic RNA of the Hepatitis C Virus is uncapped, non-polyadenylated and harbors a peculiar internal ribosome entry site (IRES) that binds the ribosome directly to the AUG codon. Thus, we have exploited the unique properties of the HCV IRES and other related IRESes (HCV-like) to study how translation initiation can be modulated by miRNAs on these elements. Here, we report that miRNA binding to the 3΄ UTR can stimulate translation of a reporter gene given that its expression is driven by an HCV-like IRES and that it lacks a poly(A) tail at its 3΄ extremity.
authors.affiliation: CIRI, International Center for Infectiology Research, Université de Lyon, 69364 Lyon, France.|INSERM, U1111, Lyon, France.|Ecole Normale Supérieure de Lyon, Lyon, France.|Université Lyon 1, Centre International de Recherche en Infectiologie, Lyon, France.|CNRS, UMR5308, Lyon, France.
authors.forename: Chloé
authors.initials: C
authors.lastname: Mengardi
authors.affiliation: CIRI, International Center for Infectiology Research, Université de Lyon, 69364 Lyon, France.|INSERM, U1111, Lyon, France.|Ecole Normale Supérieure de Lyon, Lyon, France.|Université Lyon 1, Centre International de Recherche en Infectiologie, Lyon, France.|CNRS, UMR5308, Lyon, France.
authors.forename: Taran
authors.initials: T
authors.lastname: Limousin
authors.affiliation: CIRI, International Center for Infectiology Research, Université de Lyon, 69364 Lyon, France.|INSERM, U1111, Lyon, France.|Ecole Normale Supérieure de Lyon, Lyon, France.|Université Lyon 1, Centre International de Recherche en Infectiologie, Lyon, France.|CNRS, UMR5308, Lyon, France.
authors.forename: Emiliano P
authors.initials: EP
authors.lastname: Ricci
authors.affiliation: CIRI, International Center for Infectiology Research, Université de Lyon, 69364 Lyon, France.|INSERM, U1111, Lyon, France.|Ecole Normale Supérieure de Lyon, Lyon, France.|Université Lyon 1, Centre International de Recherche en Infectiologie, Lyon, France.|CNRS, UMR5308, Lyon, France.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Soto-Rifo
authors.affiliation: CIRI, International Center for Infectiology Research, Université de Lyon, 69364 Lyon, France.|INSERM, U1111, Lyon, France.|Ecole Normale Supérieure de Lyon, Lyon, France.|Université Lyon 1, Centre International de Recherche en Infectiologie, Lyon, France.|CNRS, UMR5308, Lyon, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Decimo
authors.affiliation: CIRI, International Center for Infectiology Research, Université de Lyon, 69364 Lyon, France.|INSERM, U1111, Lyon, France.|Ecole Normale Supérieure de Lyon, Lyon, France.|Université Lyon 1, Centre International de Recherche en Infectiologie, Lyon, France.|CNRS, UMR5308, Lyon, France.
authors.forename: Théophile
authors.initials: T
authors.lastname: Ohlmann
mesh_terms: D003062:Codon / Q000235:genetics; D005786:Gene Expression Regulation; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000235:genetics / Q000821:virology; D006801:Humans; D000067556:Internal Ribosome Entry Sites / Q000235:genetics*; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D010442:Peptide Chain Initiation, Translational; D039122:Poly(A)-Binding Protein I / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics; D012367:RNA, Viral / Q000096:biosynthesis / Q000235:genetics; D054682:Ribosome Subunits, Small, Eukaryotic / Q000235:genetics
chemical_list: D003062:Codon; D000067556:Internal Ribosome Entry Sites; D035683:MicroRNAs; D039122:Poly(A)-Binding Protein I; D012367:RNA, Viral