Comprehensive search for the G-quadruplex structure in mRNA

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K14338
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 37010:Bio-related chemistry
• Research Institution: Kumamoto University
• Principal Investigator: KATSUDA YOUSUKE 熊本大学, 大学院先端科学研究部(工), 助教 (50632460)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: RNA G-quadurplex / translation

Outline of Final Research Achievements

Guanine-rich RNA sequences can form thermodynamically-stable four-stranded RNA structures known as RNA G-quadruplex (RGq). It has been long understood that RGq structrues are linked to essential biological processes, yet the physiological significance of RGq structrues in cells still remains unclear. Here, we demonstrate a method that permits the discovery of RGq structrues which affect protein translation in mammalian cells. The method is an integration of antibody array technology and a small-molecule RGB-1, which selectively stabilizes RGq structrues. By applying this technique to 84-human-cancer-related genes, we found NECTIN-4 and CAPG as two genes carrying G-quadruplex structures on the 5’UTR of their mRNA. Further investigations revealed that the RGq structrues of CAPG exhibits a structural polymorphism. This infers that the polymorphic G-quadruplex structure in the 5’UTR of the mRNA would promote environment-responsive regulation of gene expression.

Free Research Field

生体機能関連化学

Academic Significance and Societal Importance of the Research Achievements

バイオインフォマティクス技術の向上によりmRNAの構造が正確に予想すること可能になってきている。しかし近年、核酸高次構造は環境依存的に変化することが明らかになってきており、細胞内環境を具体的に数値化することが困難であることから、バイオインフォマティクスのみで細胞内の核酸高次構造を正確に予想することは困難であると考えられる。
そこで申請者はRNA G-quadaruplexに選択的に結合する化合物RGB-1を用いて細胞内RGqの網羅的な探索を可能とする技術を開発した。同手法を用いて、今まで知られていなかった遺伝子からRGqを同定することに成功した。