Regulation of expression of drug metabolizing enzymes by RNA modification

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K07013
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: Kanazawa University
• Principal Investigator: Nakano Masataka 金沢大学, 薬学系, 助教 (00816225)
• Project Period (FY): 2022-11-15 – 2024-03-31
• Keywords: 薬物代謝 / m6A修飾 / 転写後遺伝子発現制御

Outline of Final Research Achievements

Interindividual differences in the expression and activity of drug metabolizing enzymes including cytochrome P450, UDP-glucuronosyltransferase, and esterases cause variable therapeutic efficacy or adverse events of drugs. The present study revealed that methylation of adenosine at the N6 position on RNA have emerged as a novel regulator of drug metabolism potency. Elucidation of the significance of N6-methyladenosine in the regulation of drug metabolizing enzymes is expected to lead to a deeper understanding of interindividual variability in the therapeutic efficacy or adverse effects of medicines.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

薬物治療において問題となる医薬品による薬効や副作用の個人差の一因として、転写後修飾の一つであるアデノシン6位メチル化 (m6A修飾) による、ヒト肝における薬物代謝酵素の発現制御の可能性を明らかにした。本研究成果は個別化医療の実現に向けた有用な基盤情報となることが期待される。また、m6A修飾が転写後レベルのみではなくクロマチン構造などの制御を介した様々なメカニズムによって、薬物代謝酵素の発現を調節することが明らかになり、分子生物学的にも有用な知見を得ることができた。