Small molecule-based detection of non-canonical RNA G-quadruplex structures that modulate protein translation. Issue 14 (8th July 2022)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Nucleic acids research. Volume 50:Issue 14(2022)
• Page Start: 8143
• Page End: 8153
• Publication Date: 2022-07-08
• Subjects: Nucleic acids -- Periodicals; Molecular biology -- Periodicals; 572.805
• DOI: 10.1093/nar/gkac580
• Languages: English
• ISSNs: 0305-1048

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. Graphical Abstract: