Small Molecule-based Detection of Non-canonical RNA G-quadruplex Structures That Modulate Protein Translation

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2022 Jul 8

PMID 35801908

Authors

Yousuke Katsuda

Shin-Ichi Sato

Maimi Inoue

Hisashi Tsugawa

Takuto Kamura

Tomoki Kida

Rio Matsumoto

Sefan Asamitsu

Norifumi Shioda

Shuhei Shiroto

Yoshiki Oosawatsu

Kenji Yatsuzuka

Yusuke Kitamura

Masaki Hagihara

Toshihiro Ihara

Motonari Uesugi

Affiliations

Soon will be listed here.

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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