Analysis of the molecular mechanism of IgH gene diversification depending on RNA-editing by AID

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H01027
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 49:Pathology, infection/immunology, and related fields
• Research Institution: Kyoto University
• Principal Investigator: HONJO TASUKU 京都大学, 高等研究院, 特別教授 (80090504)
• Co-Investigator(Kenkyū-buntansha): 小林 牧 京都大学, 医学研究科, 特定准教授 (20400690) ; Begum NasimAra 京都大学, 医学研究科, 特定准教授 (80362507)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: AID / RNA編集 / 免疫グロブリン遺伝子 / トポイソメラーゼ 1

Outline of Final Research Achievements

We analyzed the molecular function of AID, which supports the diversification of antibody genes. Analysis of the translational repression mechanism of DNA topoisomerase 1 (Top1) which alters the secondary structure of DNA revealed that AID activation promotes miRNA-Ago2 complex binding to Top1 mRNA (particularly to 3'UTR). We have demonstrated that the function of AID during the DNA cleavage step is through the control of miRNA complex.
Furthermore, when we explored the possibility of RNA editing for the repair stage of class switch recombination that depends on the C-terminal domain of AID, we discovered a new molecular mechanism of the repair stage which depends on the protein binding to the C-terminal domain of AID.

Free Research Field

分子免疫学

Academic Significance and Societal Importance of the Research Achievements

AIDの発見以来、２０余年間、AIDの標的RNA分子を探索し、初めてmiRNAを通じたmRNAの制御がDNA切断を促進するという新しい分子メカニズムを明らかにした。抗体遺伝子組換えはワクチンを始めとする感染性制御の根幹を成す生命システムであり、その謎について新発見を得た。