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A Small Molecule That Represses Translation of G-Quadruplex-Containing mRNA

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† ‡ Institute for Integrated Cell-Material Sciences (WPI-iCeMS) and Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan
§Center for the Promotion of Excellence in Higher Education and Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan
Graduate School of Science and Technology, Hirosaki University, Hirosaki, Aomori 036-8561, Japan
Cite this: J. Am. Chem. Soc. 2016, 138, 29, 9037–9040
Publication Date (Web):July 13, 2016
Copyright © 2016 American Chemical Society

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    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.

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