A Small Molecule That Represses Translation of G-Quadruplex-Containing mRNA
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- 作者：Yousuke Katsuda ; Shin-ichi Sato ; Lisa Asano ; Yoshitaka Morimura ; Tomoyuki Furuta ; Hiroshi Sugiyama ; Masaki Hagihara ; Motonari Uesugi
- 刊名：Journal of the American Chemical Society
- 出版年：2016
- 出版时间：July 27, 2016
- 年：2016
- 卷：138
- 期：29
- 页码：9037-9040
- 全文大小：281K
- 年卷期：0
- ISSN：1520-5126
文摘
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.