Visualization of specific RNA secondary structures in vivo

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K15417
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 37030:Chemical biology-related
• Research Institution: Institute of Physical and Chemical Research (2021-2022); Kumamoto University (2020)
• Principal Investigator: Asamitsu Sefan 国立研究開発法人理化学研究所, 生命機能科学研究センター, 訪問研究員 (70849091)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: RNA高次構造 / 神経細胞 / 分子プローブ

Outline of Final Research Achievements

In this research project, to elucidate the molecular neuroscience role of the G-quadruplex (G4) structure, which is formed by sequences rich in contiguous guanines, we developed a molecular probe that can detect the G4 structure and analyzed the functions using mouse brain and primary mouse neurons. We found that messenger RNA containing the G4 structure tends to accumulate in stress granules, intracellular phase-separating compartments, by various molecular biological analyses using novel peptide probes based on single-stranded antibodies that recognize the G4 structure. Biochemical and electrophysiological analyses revealed that the G4 structure is essential for the formation of functional stress granules and plays an important role in the maintenance of neuronal homeostasis under oxidative stress.

Free Research Field

核酸機能科学

Academic Significance and Societal Importance of the Research Achievements

G4構造は、細胞内の局所環境の変化・化学修飾・相互作用因子等、多くの要因によってダイナミックな形成挙動を示す。本研究によって得られた知見を加味すると、G4構造を足掛かりとする緻密なRNA制御機構がストレス顆粒を含む多くの細胞内相分離体の機能的な形成に貢献することが示唆された。またストレス顆粒は筋萎縮性側索硬化症（ALS）等の神経変性疾患の発症要因と密接に関与している。本研究成果はストレスが関与する多くの疾患の治療薬開発の一助となることが期待される。