RNA degradation in antiviral immunity and autoimmunity

Trends Immunol. 2015 Mar;36(3):179-88. doi: 10.1016/j.it.2015.02.001. Epub 2015 Feb 20.


Post-transcriptional control determines the fate of cellular RNA molecules. Nonsense-mediated decay (NMD) provides quality control of mRNA, targeting faulty cellular transcripts for degradation by multiple nucleases including the RNA exosome. Recent findings have revealed a role for NMD in targeting viral RNA molecules, thereby restricting virus infection. Interestingly, NMD is also linked to immune responses at another level: mutations affecting the NMD or RNA exosome machineries cause chronic activation of defence programmes, resulting in autoimmune phenotypes. Here we place these observations in the context of other links between innate antiviral immunity and type I interferon mediated disease and examine two models: one in which expression or function of pathogen sensors is perturbed and one wherein host-derived RNA molecules with a propensity to activate such sensors accumulate.

Keywords: Aicardi-Goutières syndrome; MDA5; RNA exosome; nonsense-mediated decay; pattern-recognition receptor; type I interferon.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Autoimmune Diseases of the Nervous System / genetics
  • Autoimmune Diseases of the Nervous System / immunology
  • Autoimmune Diseases of the Nervous System / pathology
  • Autoimmunity
  • Endoribonucleases / immunology
  • Endoribonucleases / metabolism
  • Exosome Multienzyme Ribonuclease Complex / immunology
  • Host-Pathogen Interactions
  • Humans
  • Immunity, Innate*
  • Interferon Type I / genetics
  • Interferon Type I / immunology*
  • Lupus Erythematosus, Systemic / genetics
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Erythematosus, Systemic / pathology
  • Nervous System Malformations / genetics
  • Nervous System Malformations / immunology
  • Nervous System Malformations / pathology
  • Nonsense Mediated mRNA Decay / immunology*
  • RNA, Viral / immunology*
  • RNA, Viral / metabolism
  • Signal Transduction
  • Viruses / immunology*


  • Interferon Type I
  • RNA, Viral
  • Endoribonucleases
  • Exosome Multienzyme Ribonuclease Complex

Supplementary concepts

  • Aicardi-Goutieres syndrome