Reguratory role of RNase Reganse-1 in inflammatory response through its phosphorylation

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K15189
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: Osaka University
• Principal Investigator: Hiroki Tanaka 大阪大学, 免疫学フロンティア研究センター, 特任助教(常勤) (50747920)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: mRNA分解酵素 / Regnase-1 / mRNA安定性 / 炎症

Outline of Final Research Achievements

Regnase-1is an endoribonuclease that regulates immune response through its enzymatic activity. Regnase-1 is induced upon stimulation with TLR ligands or proinflammatory cytokines, and degrades inflammation-associated mRNAs, thereby forming a negative feedback circuit to diminish excess inflammatory response. In this grant, I focused on inactivation mechanism of Regnase-1 mediated by proinflammatory cytokine Interleukin-17 and tried to elucidate the molecular mechanism of this inactivation. And I found that Regnase-1 phosphorylation resulted in a change in subcellular localization of Regnase-1 proteins from the endoplasmic reticulum to the cytosols. This translocation leads to attenuation of the RNase activity of Regnase-1. These results suggest that Regnase-1 phosphorylation is important for fine-tuning of the expression levels of IL-17-associated inflammatory genes and controlling IL-17-mediated inflammatory diseases.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究では、Rengnase-1遺伝子がインターロイキン１７の関与する慢性炎症疾患の症状を制御する重要な因子であり、インターロイキン１７による細胞刺激によって誘発されるRegnase-1蛋白質のリン酸化が炎症状態の維持における鍵となる現象であることを明らかにした。またRegnase-1のリン酸化の阻害は、これらの疾患を治療する有力なストラテジーとなり得ることを示した。