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

RNA degradation in antiviral immunity and autoimmunity.

Author information

1
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.
2
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.

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.

KEYWORDS:

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

PMID:
25709093
PMCID:
PMC4358841
DOI:
10.1016/j.it.2015.02.001
[Indexed for MEDLINE]
Free PMC Article

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