Control of RNA modification aimed at antivirus activities

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H02850
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 37030:Chemical biology-related
• Research Institution: Kyoto University
• Principal Investigator: Imanishi Miki 京都大学, 化学研究所, 准教授 (80362391)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: RNAメチル化 / 脱メチル化酵素 / 非標準核酸構造 / エピトランスクリプトーム

Outline of Final Research Achievements

In recent years, it has become clear that RNA methylation is involved in the viral infection process, thus selective compounds or molecules that regulate methylation are expected to be useful against viral infection. In addition, knowledge on the mechanism of RNA methylation of viral genomes is also lacking. In this study, we used an original screening system to find selective inhibitor candidates for an N6-methyladenosine demethylase, FTO. We also found that RNA methyltransferases recognize RNA nonstandard structures, providing experimental support for the relationship between RNA nonstandard structures and RNA methylation in viral genomes that had been suggested by bioinformatics analysis.

Free Research Field

生物分子化学

Academic Significance and Societal Importance of the Research Achievements

近年、ウイルスの感染過程でRNAのメチル化が関わることが示唆されているため、本研究で見出した新規な骨格および阻害様式をもつ脱メチル化酵素阻害剤によってRNAのメチル化状態を変化させることは、新しい抗ウイルス薬開発の基盤となることが期待される。また、ウイルスゲノムにおけるRNA非標準構造とRNAメチル化との関係性を実験的に支持する結果を得たことから、抗ウイルスのための新たな方向性を提起できたといえる。