Elucidation of the regulatory mechanisms of RNA granule dynamics and its application to treatment of intractable diseases

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K06494
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43010:Molecular biology-related
• Research Institution: Kindai University
• Principal Investigator: Satoh Ryosuke 近畿大学, 薬学部, 講師 (00635592)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: RNA顆粒 / ストレス顆粒 / 分裂酵母 / 液ー液相分離 / LLPS / PUF / イノシトールリン脂質

Outline of Final Research Achievements

I launched and conducted a screening system using a fission yeast cell death phenotype associated with the overexpression of RNA granule regulators to isolate genes and compounds that affect the dynamics of RNA granule formation and disassembly. As a result, the fission yeast C kinase Pck2 is sequestrated into stress granules in a kinase activity-dependent manner under heat shock conditions. Furthermore, through this screening system, compounds that have the potential to promote or suppress stress granule formation were identified. Regulating the formation of RNA granules, including stress granules, with these compounds may provide a novel therapeutic strategy for diseases associated with abnormal RNA granule formation.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

ストレス顆粒（SG）やP-bodyといったRNA顆粒は、液-液相分離（LLPS）を介して局所かつ時期特異的にRNA代謝や翻訳調節、さらにはシグナル伝達制御を行う場であり、がんや神経変性疾患の発症と密接に関わる。特に、異常なRNA顆粒形成と深く関連するALSやアルツハイマー病といった難治性神経変性疾患については、根本的な治療法がないのが現状である。本研究を推進することにより、RNA顆粒ダイナミクスを標的とした革新的な作用機序をもつ「がんや神経変性疾患の治療薬開発」に貢献できると考えられる。