Study of mRNA translation in immune system

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03488
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: Kyoto University
• Principal Investigator: Mino Takahsi 京都大学, 医学研究科, 助教 (60646149)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 免疫 / サイトカイン / 転写後制御 / 翻訳 / mRNA分解 / Regnase-1 / UPF1

Outline of Final Research Achievements

Post-transcriptional regulation that modifies mRNA stability and translation provides rapid and flexible control of gene expression in immune system. Regnase-1-mediated mRNA decay (RMD), in which inflammatory mRNAs harboring specific stem-loop structures are degraded, is a critical part of proper immune homeostasis. However, the mechanisms of the RMD remain to be clarified. This study is aiming to investigate molecular mechanism of mRNA regulation and translation mediated by RMD. We found that Regnase-1 targets pioneer rounds of translation and is critical for rapid resolution of inflammation through restriction of the number of proteins translated by a given mRNA. Our findings reveal that RMD is essential for efficiently degrading inflammatory mRNAs undergoing pioneer rounds of translation.

Free Research Field

免疫学，分子生物学

Academic Significance and Societal Importance of the Research Achievements

炎症は，病原体の排除に重要な免疫反応であるが，過剰な炎症は敗血症性ショックや自己免疫疾患，動脈硬化，代謝性疾患など様々な病気の原因である。この炎症応答の厳密な制御にRNA制御が重要であることが近年明らかとなってきたが，その分子メカニズムは不明であった。本研究は，Regnase-1によるパイオニアラウンド翻訳が生じているmRNA分解が免疫制御に重要であることを解明した。本研究の成果は，過剰もしくは慢性的な炎症で生じる炎症性疾患の病態解明や，ワクチンの効果を高める添加剤(ワクチンアジュバント)の開発など，新たな治療法の開発につながることが期待される。