Structural probing of RNA G-quadruplex structures in vivo

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K05314
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 37030:Chemical biology-related
• Research Institution: University of Miyazaki
• Principal Investigator: Ishizuka Takumi 宮崎大学, 医学部, 学部講師 (50700085)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: グアニン四重鎖 / RNA / セリウム

Outline of Final Research Achievements

RNA G-quadruplexes (rG4) have important biological roles and are expected as an attractive therapeutic target for drug design. The structural analysis of rG4 provides significant information for a better understanding of the function of rG4. We found that Ce(IV)/EDTA complex as a molecular scissor that can be effectively and selectively cleaved specific position of nucleotides in rG4. We demonstrated that the loop regions of rG4 are specifically cleaved by the Ce(IV)/EDTA complex. This strategy provides a useful method to probe rG4 at nucleotide resolution. The current study is the first step in providing insight into the structure-dependent Ce(IV)/EDTA reactivity in rG4. The method will likely make possible facile nucleotide resolution analysis of RNA structures and provides a concept for targeting rG4 related to disease.

Free Research Field

核酸化学

Academic Significance and Societal Importance of the Research Achievements

rG4は神経疾患に関与しており、今回開発したrG4解析法は、形成メカニズムをはじめとした未解明の機能の理解が進むものと期待される。Ce(IV)/EDTA錯体の生体親和性を考慮するとin vivoでのrG4の解析が可能であり、本手法を利用した診断法への応用も期待できる。