TRIM4 modulates type I interferon induction and cellular antiviral response by targeting RIG-I for K63-linked ubiquitination

J Mol Cell Biol. 2014 Apr;6(2):154-63. doi: 10.1093/jmcb/mju005.

Abstract

RIG-I is a pivotal cytoplasmic sensor that recognizes different species of viral RNAs. This recognition leads to activation of the transcription factors NF-κB and IRF3, which collaborate to induce type I interferons (IFNs) and innate antiviral response. In this study, we identified the TRIM family protein TRIM4 as a positive regulator of RIG-I-mediated IFN induction. Overexpression of TRIM4 potentiated virus-triggered activation of IRF3 and NF-κB, as well as IFN-β induction, whereas knockdown of TRIM4 had opposite effects. Mechanistically, TRIM4 associates with RIG-I and targets it for K63-linked polyubiquitination. Our findings demonstrate that TRIM4 is an important regulator of the virus-induced IFN induction pathways by mediating RIG-I for K63-linked ubiquitination.

Keywords: RIG-I; TRIM4; antiviral response; type I interferon; ubiquitination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / metabolism*
  • Cell Line
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / metabolism*
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Humans
  • Interferon-beta / pharmacology*
  • Lysine / metabolism*
  • Polyubiquitin / metabolism
  • Protein Binding / drug effects
  • Receptors, Immunologic
  • Sendai virus / drug effects
  • Sendai virus / physiology*
  • Signal Transduction / drug effects
  • Transcription Factors / metabolism
  • Tripartite Motif Proteins
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitination / drug effects*

Substances

  • Carrier Proteins
  • Receptors, Immunologic
  • Transcription Factors
  • Tripartite Motif Proteins
  • Polyubiquitin
  • Interferon-beta
  • TRIM25 protein, human
  • Ubiquitin-Protein Ligases
  • RIGI protein, human
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases
  • Lysine