Protein kinase PKR and RNA adenosine deaminase ADAR1: new roles for old players as modulators of the interferon response

Curr Opin Immunol. 2011 Oct;23(5):573-82. doi: 10.1016/j.coi.2011.08.009. Epub 2011 Sep 15.

Abstract

Double-stranded RNA (dsRNA) plays a centrally important role in antiviral innate immunity, both for the production of interferon (IFN) and also in the actions of IFN. Among the IFN-inducible gene products are the protein kinase regulated by RNA (PKR) and the adenosine deaminase acting on RNA 1 (ADAR1). PKR is an established key player in the antiviral actions of IFN, through dsRNA-dependent activation and subsequent phosphorylation of protein synthesis initiation factor eIF2α thereby altering the translational pattern in cells. In addition, PKR plays an important role as a positive effector that amplifies the production of IFN. ADAR1 catalyzes the deamination of adenosine (A) in RNA with double-stranded (ds) character, leading to the destabilization of RNA duplex structures and genetic recoding. By contrast to the antiviral and proapoptotic functions associated with PKR, the actions of ADAR1 in some instances are proviral and cell protective as ADAR1 functions as a suppressor of dsRNA-mediated antiviral responses including activation of PKR and interferon regulatory factor 3.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosine / metabolism
  • Adenosine Deaminase / genetics
  • Adenosine Deaminase / immunology*
  • Adenosine Deaminase / metabolism
  • Animals
  • Eukaryotic Initiation Factor-2 / genetics
  • Eukaryotic Initiation Factor-2 / immunology
  • Eukaryotic Initiation Factor-2 / metabolism
  • Gene Expression Regulation / immunology*
  • Humans
  • Immunity, Innate*
  • Interferon Regulatory Factor-3 / genetics
  • Interferon Regulatory Factor-3 / immunology
  • Interferon Regulatory Factor-3 / metabolism
  • Interferons / genetics
  • Interferons / immunology
  • Interferons / metabolism
  • Mice
  • Phosphorylation
  • Protein Structure, Tertiary
  • RNA Virus Infections / genetics
  • RNA Virus Infections / immunology*
  • RNA Virus Infections / virology
  • RNA Viruses / immunology
  • RNA, Double-Stranded / immunology*
  • RNA, Viral / immunology
  • Signal Transduction / immunology*
  • eIF-2 Kinase / genetics
  • eIF-2 Kinase / immunology*
  • eIF-2 Kinase / metabolism

Substances

  • Eukaryotic Initiation Factor-2
  • IRF3 protein, human
  • Interferon Regulatory Factor-3
  • RNA, Double-Stranded
  • RNA, Viral
  • Interferons
  • eIF-2 Kinase
  • Adenosine Deaminase
  • Adenosine