The double-stranded RNA-binding protein PACT functions as a cellular activator of RIG-I to facilitate innate antiviral response

Cell Host Microbe. 2011 Apr 21;9(4):299-309. doi: 10.1016/j.chom.2011.03.007.

Abstract

RIG-I, a virus sensor that triggers innate antiviral response, is a DExD/H box RNA helicase bearing structural similarity with Dicer, an RNase III-type nuclease that mediates RNA interference. Dicer requires double-stranded RNA-binding protein partners, such as PACT, for optimal activity. Here we show that PACT physically binds to the C-terminal repression domain of RIG-I and potently stimulates RIG-I-induced type I interferon production. PACT potentiates the activation of RIG-I by poly(I:C) of intermediate length. PACT also cooperates with RIG-I to sustain the activation of antiviral defense. Depletion of PACT substantially attenuates viral induction of interferons. The activation of RIG-I by PACT does not require double-stranded RNA-dependent protein kinase or Dicer, but is mediated by a direct interaction that leads to stimulation of its ATPase activity. Our findings reveal PACT as an important component in initiating and sustaining the RIG-I-dependent antiviral response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chlorocebus aethiops
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / immunology
  • DEAD-box RNA Helicases / metabolism*
  • HEK293 Cells
  • Humans
  • Immunity, Innate
  • Interferon Type I / biosynthesis
  • Mice
  • Plasmids / genetics
  • Poly I-C / immunology
  • RNA Interference
  • RNA, Double-Stranded / metabolism
  • RNA, Small Interfering
  • RNA-Binding Proteins / metabolism*
  • Signal Transduction / physiology
  • Vero Cells
  • Viruses / immunology*
  • Viruses / metabolism
  • eIF-2 Kinase / metabolism
  • eIF-2 Kinase / physiology

Substances

  • Interferon Type I
  • PRKRA protein, human
  • RNA, Double-Stranded
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • eIF-2 Kinase
  • DDX58 protein, human
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases
  • Poly I-C