title: A Small Molecule That Represses Translation of G-Quadruplex-Containing mRNA.
abstract: The G-quadruplexes form highly stable nucleic acid structures, which are implicated in various biological processes in both DNA and RNA. Although DNA G-quadruplexes have been studied in great detail, biological roles of RNA G-quadruplexes have received less attention. Here, a screening of a chemical library permitted identification of a small-molecule tool that binds selectively to RNA G-quadruplex structures. The polyaromatic molecule, RGB-1, stabilizes RNA G-quadruplex, but not DNA versions or other RNA structures. RGB-1 intensified the G-quadruplex-mediated inhibition of RNA translation in mammalian cells, decreased expression of the NRAS proto-oncogene in breast cancer cells, and permitted identification of a novel sequence that forms G-quadruplex in NRAS mRNA. RGB-1 may serve as a unique tool for understanding cellular roles of RNA G-quadruplex structures.
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Katsuda
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Sato
authors.forename: Lisa
authors.initials: L
authors.lastname: Asano
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Morimura
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Furuta
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sugiyama
authors.affiliation: Graduate School of Science and Technology, Hirosaki University , Hirosaki, Aomori 036-8561, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Hagihara
authors.forename: Motonari
authors.initials: M
authors.lastname: Uesugi
mesh_terms: D004353:Drug Evaluation, Preclinical; D054856:G-Quadruplexes; D014176:Protein Biosynthesis / Q000187:drug effects*; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D054852:Small Molecule Libraries / Q000494:pharmacology*
chemical_list: D012333:RNA, Messenger; D054852:Small Molecule Libraries