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

Y. Katsuda,Shin-ichi Sato,M. Inoue,Hisashi Tsugawa,Takuto Kamura,Tomoki Kida,Rio Matsumoto,Sefan Asamitsu,N. Shioda,Shuhei Shiroto,Yoshiki Oosawatsu,Kenji Yatsuzuka,Yusuke Kitamura,M. Hagihara,T. Ihara,M. Uesugi

Published 2022 in Nucleic Acids Research

ABSTRACT

Abstract 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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