title: The mitochondrial targeting chaperone 14-3-3ε regulates a RIG-I translocon that mediates membrane association and innate antiviral immunity.
abstract: RIG-I is a cytosolic pathogen recognition receptor that initiates immune responses against RNA viruses. Upon viral RNA recognition, antiviral signaling requires RIG-I redistribution from the cytosol to membranes where it binds the adaptor protein, MAVS. Here we identify the mitochondrial targeting chaperone protein, 14-3-3ε, as a RIG-I-binding partner and essential component of a translocation complex or "translocon" containing RIG-I, 14-3-3ε, and the TRIM25 ubiquitin ligase. The RIG-I translocon directs RIG-I redistribution from the cytosol to membranes where it mediates MAVS-dependent innate immune signaling during acute RNA virus infection. 14-3-3ε is essential for the stable interaction of RIG-I with TRIM25, which facilitates RIG-I ubiquitination and initiation of innate immunity against hepatitis C virus and other pathogenic RNA viruses. Our results define 14-3-3ε as a key component of a RIG-I translocon required for innate antiviral immunity.
authors.affiliation: Department of Immunology, University of Washington School of Medicine, Seattle, WA 98195-7950, USA.
authors.forename: Helene Minyi
authors.initials: HM
authors.lastname: Liu
authors.forename: Yueh-Ming
authors.initials: YM
authors.lastname: Loo
authors.forename: Stacy M
authors.initials: SM
authors.lastname: Horner
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Zornetzer
authors.forename: Michael G
authors.initials: MG
authors.lastname: Katze
authors.forename: Michael
authors.initials: M
authors.lastname: Gale
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D002460:Cell Line; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D016174:Hepacivirus / Q000276:immunology; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008954:Models, Biological; D018832:Molecular Chaperones / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D011971:Receptors, Immunologic; D014157:Transcription Factors / Q000378:metabolism*; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D048948:14-3-3 Proteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D011971:Receptors, Immunologic; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; C084523:TRIM25 protein, human; D044767:Ubiquitin-Protein Ligases; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases