The mitochondrial targeting chaperone 14-3-3ε regulates a RIG-I translocon that mediates membrane association and innate antiviral immunity

Cell Host Microbe. 2012 May 17;11(5):528-37. doi: 10.1016/j.chom.2012.04.006.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 14-3-3 Proteins / metabolism*
  • Cell Line
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / metabolism*
  • Hepacivirus / immunology
  • Humans
  • Membrane Proteins / metabolism*
  • Models, Biological
  • Molecular Chaperones / metabolism*
  • Protein Binding
  • Protein Interaction Mapping
  • Receptors, Immunologic
  • Transcription Factors / metabolism*
  • Tripartite Motif Proteins
  • Ubiquitin-Protein Ligases / metabolism*

Substances

  • 14-3-3 Proteins
  • Membrane Proteins
  • Molecular Chaperones
  • Receptors, Immunologic
  • Transcription Factors
  • Tripartite Motif Proteins
  • TRIM25 protein, human
  • Ubiquitin-Protein Ligases
  • RIGI protein, human
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases