RNA degradation in antiviral immunity and autoimmunity.
Bottom Line: 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.
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.Show MeSH
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Mentions: NMD is a highly conserved mRNA surveillance pathway and has been reviewed in detail elsewhere [5–8]. Here, we will discuss only the basic principles of NMD (Figure 1). NMD detects mRNAs harbouring premature translation termination codons (PTCs) and then targets these transcripts for degradation. PTCs can arise as a consequence of gene mutations or errors during transcription. If translated, PTC-containing mRNAs encode C-terminally truncated proteins. Such aberrant proteins can have adverse effects; for example, truncation may result in dominant-negative function. NMD therefore serves an important role in that it ensures that only intact mRNAs are translated.
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.