Development of a sequence and stimulation dependent regulation method of epitranscriptome and its application to biological clock

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K19046
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 37:Biomolecular chemistry and related fields
• Research Institution: Kyoto University
• Principal Investigator: Imanishi Miki 京都大学, 化学研究所, 准教授 (80362391)
• Project Period (FY): 2021-07-09 – 2023-03-31
• Keywords: RNAメチル化 / RNA結合タンパク質

Outline of Final Research Achievements

In recent years, the importance of RNA-targeted regulation has increased. Among them, one of the post-transcriptional modifications, N6 methyladenosine (m6A), has attracted attention as an important modifying base that determines development, cancer, and circadian clock cycles, etc. Therefore, these methods are limited in their ability to analyze a wide variety of RNA methylation roles. In this study, we constructed a system to switch the function of RNA methyltransferase regulatory enzymes by external environmental changes and to control methylation in a sequence-selective manner.

Free Research Field

生物分子化学

Academic Significance and Societal Importance of the Research Achievements

m6Aが発生やガン化、体内時計、ウイルス感染などに関わることが最近報告され、その生物学的重要性と創薬標的としての可能性が高まりつつある。一方、m6A研究の手段は、酵素阻害剤の利用、酵素の発現抑制、過剰発現に限られ、個々のサイトのメチル化状態を制御する方法がなかった。RNAメチル化の役割はスプライシング、安定性、翻訳、mRNA輸送と多岐にわたるため、標的選択的に適切なタイミングでRNAメチル化状態を制御する方法論の構築は、様々な生命現象の解明やエピトランスクリプトームを標的とする創薬研究の飛躍的な進展につながることが期待される。