title: RNA degradation in antiviral immunity and autoimmunity.
abstract: 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.
authors.affiliation: Medical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Rigby
authors.affiliation: Medical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK. Electronic address: jan.rehwinkel@imm.ox.ac.uk.
authors.forename: Jan
authors.initials: J
authors.lastname: Rehwinkel
mesh_terms: D020274:Autoimmune Diseases of the Nervous System / Q000235:genetics / Q000276:immunology / Q000473:pathology; D015551:Autoimmunity; D004722:Endoribonucleases / Q000276:immunology / Q000378:metabolism; D063326:Exosome Multienzyme Ribonuclease Complex / Q000276:immunology; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology / Q000473:pathology; D009421:Nervous System Malformations / Q000235:genetics / Q000276:immunology / Q000473:pathology; D059365:Nonsense Mediated mRNA Decay / Q000276:immunology*; D012367:RNA, Viral / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D014780:Viruses / Q000276:immunology*
chemical_list: D007370:Interferon Type I; D012367:RNA, Viral; D004722:Endoribonucleases; D063326:Exosome Multienzyme Ribonuclease Complex
keywords: Aicardi-Goutières syndrome; MDA5; RNA exosome; nonsense-mediated decay; pattern-recognition receptor; type I interferon