Novel regulatory mechanism of skeletal muscle mass via protein methylation

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07315
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48040:Medical biochemistry-related
• Research Institution: Fujita Health University
• Principal Investigator: Hitachi Keisuke 藤田医科大学, 医科学研究センター, 講師 (10508469)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: メチル化修飾 / 骨格筋 / 筋疾患 / 筋萎縮

Outline of Final Research Achievements

I have investigated the role of Mettl21e in regulating skeletal muscle mass by analyzing knockout mice of Mettl21e and knock-in mice of its target protein. Through this study, I have successfully elucidated the molecular mechanism underlying the methylation by Mettl21e. Additionally, my focus on Mettl21e has allowed me to shed light on the previously unclear relationship between methylation and human muscle disorders. Furthermore, during the generation of knock-in mice, I obtained double knockout mice of myosin. The analysis of these mice has revealed a potential association between fast-twitch myosin and human muscle disorder.

Free Research Field

医科学一般

Academic Significance and Societal Importance of the Research Achievements

Mettl21eによるタンパク質のメチル化修飾を介した骨格筋量の制御メカニズムは、従来のタンパク質分解・合成の枠に囚われない新たな筋量制御機構である可能性を見出すことができた。また、ヒト筋疾患サンプルにおいてもメチル化修飾が変化していることが見出せた。よって本研究により、タンパク質のメチル化修飾を基軸とすることでヒトの筋萎縮・筋疾患に対する新たな治療戦略を構築することが可能になると考えられる。