Establishing the role of ATP for the function of the RIG-I innate immune sensor

Elife. 2015 Sep 15;4:e09391. doi: 10.7554/eLife.09391.

Abstract

Retinoic acid-inducible gene I (RIG-I) initiates a rapid innate immune response upon detection and binding to viral ribonucleic acid (RNA). This signal activation occurs only when pathogenic RNA is identified, despite the ability of RIG-I to bind endogenous RNA while surveying the cytoplasm. Here we show that ATP binding and hydrolysis by RIG-I play a key role in the identification of viral targets and the activation of signaling. Using biochemical and cell-based assays together with mutagenesis, we show that ATP binding, and not hydrolysis, is required for RIG-I signaling on viral RNA. However, we show that ATP hydrolysis does provide an important function by recycling RIG-I and promoting its dissociation from non-pathogenic RNA. This activity provides a valuable proof-reading mechanism that enhances specificity and prevents an antiviral response upon encounter with host RNA molecules.

Keywords: RIG-I like receptor; RNA helicase; antiviral signaling; biochemistry; immunology; innate immunity; none.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Cell Line
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / metabolism*
  • Humans
  • Hydrolysis
  • Immunity, Innate*
  • Protein Binding
  • RNA, Viral / metabolism*
  • Signal Transduction*

Substances

  • RNA, Viral
  • Adenosine Triphosphate
  • DDX58 protein, human
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases