| Literature DB >> 27595231 |
Eun-Young Lee1, Hyun-Cheol Lee2, Hyun-Kwan Kim1,2, Song Yee Jang1, Seong-Jun Park3, Yong-Hoon Kim4, Jong Hwan Kim5, Jungwon Hwang1, Jae-Hoon Kim2, Tae-Hwan Kim2, Abul Arif6, Seon-Young Kim5, Young-Ki Choi7, Cheolju Lee3,8, Chul-Ho Lee4, Jae U Jung9, Paul L Fox6, Sunghoon Kim10, Jong-Soo Lee2, Myung Hee Kim1,11.
Abstract
The mammalian cytoplasmic multi-tRNA synthetase complex (MSC) is a depot system that regulates non-translational cellular functions. Here we found that the MSC component glutamyl-prolyl-tRNA synthetase (EPRS) switched its function following viral infection and exhibited potent antiviral activity. 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 mitochondrial antiviral signaling protein (MAVS) that is critical for antiviral immunity. This interaction blocked PCBP2-mediated ubiquitination of MAVS and ultimately suppressed viral replication. EPRS-haploid (Eprs+/-) mice showed enhanced viremia and inflammation and delayed viral clearance. This stimulus-inducible activation of MAVS by EPRS suggests an unexpected role for the MSC as a regulator of immune responses to viral infection.Entities:
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Year: 2016 PMID： 27595231 PMCID： PMC5173487 DOI： 10.1038/ni.3542
Source DB: PubMed Journal: Nat Immunol ISSN： 1529-2908 Impact factor: 25.606