Lee, Eun-Young Lee, Hyun-Cheol Kim, Hyun-Kwan Jang, Song Yee Park, Seong-Jun Kim, Yong-Hoon Kim, Jong Hwan Hwang, Jungwon Kim, Jae-Hoon Kim, Tae-Hwan Abul Arif Kim, Seon-Young Choi, Young-Ki Lee, Cheolju Lee, Chul-Ho Jung, Jae U. Fox, Paul L. Kim, Sunghoon Lee, Jong-Soo Kim, Myung Hee 2024-01-20T03:02:05Z 2024-01-20T03:02:05Z 2021-09-05 2016-11 1529-2908 https://pubs.kist.re.kr/handle/201004/123471 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. English NATURE PUBLISHING GROUP RIG-I TRANSLATIONAL CONTROL INNATE IMMUNITY NONCANONICAL FUNCTION INTERFERON-GAMMA MAVS DEGRADATION UBIQUITIN LIGASE RESPONSES COMPLEX BINDING Infection-specific phosphorylation of glutamyl-prolyl tRNA synthetase induces antiviral immunity Article 10.1038/ni.3542 1 NATURE IMMUNOLOGY, v.17, no.11, pp.1252 - 1262 NATURE IMMUNOLOGY 17 11 1252 1262 scie scopus 000386193200005 2-s2.0-84991574461 Immunology Immunology Article RIG-I TRANSLATIONAL CONTROL INNATE IMMUNITY NONCANONICAL FUNCTION INTERFERON-GAMMA MAVS DEGRADATION UBIQUITIN LIGASE RESPONSES COMPLEX BINDING