Post-translational modification by symmetric ariginine dimetylation in immune regulation and diseases

2016 Fiscal Year Final Research Report

• Project/Area Number: 25293066
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Showa University (2015-2016); The University of Tokyo (2014); Tokyo Medical and Dental University (2013)
• Principal Investigator: Koga Takako 昭和大学, 歯学部, 講師 (90451905)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: 破骨細胞 / 免疫系細胞 / タンパク質翻訳後修飾 / 生体恒常性

Outline of Final Research Achievements

Protein arginine methylation is a post-translational modification which contributes to a wide range of biological processes such as transcriptional control and mRNA splicing. Mice lacking PRMT5 specifically in osteoclasts showed an decreased bone mass due to an increased bone resorption. In addition, T cell-specific deletion of the Prmt5 gene led to a marked reduction in gamma chain family cytokine signaling and a severe loss of thymic iNKT cells and a decreased number of peripheral CD4+ and CD8+ T cells. PRMT5 induces the symmetric dimethylation of Sm proteins which promote the splicing of the Il2rg pre-mRNA, critically contributing to the expression of gamma chain. These findings demonstrate that arginine methylation plays a key role in the regulation of gamma chain family cytokine signaling strength by facilitating the expression of signal-transducing components.

Free Research Field

骨免疫学