濡木研公開ラボセミナー

Immunoregulatory Role of Multi-tRNA Synthetase Complex against Infection

Myung Hee Kim博士(Infection and Immunity Research Laboratory, Metabolic Regulation Research Center)

2018年01月18日(Thu)    15:30-16:00  理学部3号館 326号室   

The mammalian cytoplasmic multi-tRNA synthetase complex (MSC) is a stimulus-dependent depot system that regulates non-translational functions. It is organized by nine aminoacyl-tRNA synthetases in association with three auxiliary proteins. Under stress conditions, some MSC components are released from the complex through their post-translational modifications to provide various cellular functions including inflammation, angiogenesis and tumorigenesis. Recently, we found that MSC acts as an immunoregulatory system against viral infection. Specifically, the MSC component, glutamyl-prolyl-tRNA synthetase (EPRS), switches its function upon viral infection and exhibits potent antiviral activity. RNA virus infection-specific phosphorylation of EPRS at Ser990 induced its dissociation from the MSC, after which it was guided to the antiviral signaling pathway, where it interacted with PCBP2, a negative regulator of MAVS critical in antiviral immunity. This interaction blocked PCBP2-mediated ubiquitination of MAVS and ultimately suppressed virus replication. Collectively, this newly identified function of EPRS suggests the functional importance of the MSC as a regulator of immune responses to infection.