title: An RNA G-quadruplex is essential for cap-independent translation initiation in human VEGF IRES.
abstract: RNA G-quadruplexes located within the 5'-UTR of mRNA are almost always known to be associated with repression of cap-dependent translation. However, in this report we present functional as well as structural evidence that sequence redundancy in a G-rich segment within the 5'-UTR of human VEGF mRNA supports a 'switchable' RNA G-quadruplex structure that is essential for IRES-mediated translation initiation. Additionally, utilization of a specific combination of G-tracts within this segment allows for the conformational switch that implies a tunable regulatory role of the quadruplex structure in translation initiation. A sequence engineered from a functionally handicapped mutant moderately rescued the activity, further indicating the importance of G-quadruplex structure for VEGF IRES-A function. This to our knowledge is the first report of a conformationally flexible RNA G-quadruplex which is essential for IRES-mediated translation initiation.
authors.affiliation: Department of Chemistry and Biochemistry, Kent State University, Kent, Ohio 44242, United States.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Morris
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Negishi
authors.forename: Cathy
authors.initials: C
authors.lastname: Pazsint
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Schonhoft
authors.forename: Soumitra
authors.initials: S
authors.lastname: Basu
mesh_terms: D000818:Animals; D001483:Base Sequence; D002417:Cattle; D039603:Eukaryotic Initiation Factor-4G / Q000737:chemistry*; D054856:G-Quadruplexes; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D010442:Peptide Chain Initiation, Translational; D042442:Vascular Endothelial Growth Factors
chemical_list: D039603:Eukaryotic Initiation Factor-4G; D042442:Vascular Endothelial Growth Factors