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Small molecule-based detection of non-canonical RNA G-quadruplex structures that modulate protein translation

Katsuda, Yousuke Sato, Shin-ichi Inoue, Maimi Tsugawa, Hisashi Kamura, Takuto Kida, Tomoki Matsumoto, Rio Asamitsu, Sefan Shioda, Norifumi Shiroto, Shuhei Oosawatsu, Yoshiki Yatsuzuka, Kenji Kitamura, Yusuke Hagihara, Masaki Ihara, Toshihiro Uesugi, Motonari 京都大学 DOI:10.1093/nar/gkac580

2022.08.12

概要

Tandem repeats of guanine-rich sequences in RNA often form thermodynamically stable four-stranded RNA structures. Such RNA G-quadruplexes have long been considered to be linked to essential biological processes, yet their physiological significance in cells remains unclear. Here, we report a approach that permits the detection of RNA G-quadruplex structures that modulate protein translation in mammalian cells. The approach combines antibody arrays and RGB-1, a small molecule that selectively stabilizes RNA G-quadruplex structures. Analysis of the protein and mRNA products of 84 cancer-related human genes identified Nectin-4 and CapG as G-quadruplex-controlled genes whose mRNAs harbor non-canonical G-quadruplex structures on their 5′UTR region. Further investigations revealed that the RNA G-quadruplex of CapG exhibits a structural polymorphism, suggesting a possible mechanism that ensures the translation repression in a KCl concentration range of 25–100 mM. The approach described in the present study sets the stage for further discoveries of RNA G-quadruplexes.

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