The RNA-Editing Enzyme ADAR1 Controls Innate Immune Responses to RNA
- Mannion, Niamh M. (MRC Human Genetics Unit, IGMM, University of Edinburgh)
- Greenwood, Sam M. (MRC Human Genetics Unit, IGMM, University of Edinburgh)
- Jantsch, Michael F. (Department of Chromosome Biology, Centre for Molecular Biology, University of Vienna)
- Dorin, Julia (MRC Human Genetics Unit, IGMM, University of Edinburgh)
- Adams, Ian R. (MRC Human Genetics Unit, IGMM, University of Edinburgh)
- Scadden, A.D.J. (Department of Biochemistry, University of Cambridge)
- Öhman, Marie (Department of Molecular Biosciences, Wenner Gren Institute, Stockholm University)
- Keegan, Liam P. (MRC Human Genetics Unit, IGMM, University of Edinburgh)
- O’Connell, Mary A. (MRC Human Genetics Unit, IGMM, University of Edinburgh)
- Young, Robert (MRC Human Genetics Unit, IGMM, University of Edinburgh)
- Cox, Sarah (MRC Human Genetics Unit, IGMM, University of Edinburgh)
- Brindle, James (MRC Human Genetics Unit, IGMM, University of Edinburgh)
- Read, David (MRC Human Genetics Unit, IGMM, University of Edinburgh)
- Nellåker, Christoffer (MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford)
- Vesely, Cornelia (Department of Chromosome Biology, Centre for Molecular Biology, University of Vienna)
- Ponting, Chris P. (MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford)
- McLaughlin, Paul J. (Institute of Structural and Molecular Biology, School of Biological Sciences, Edinburgh)
DOIAbstract
The ADAR RNA-editing enzymes deaminate adenosine bases to inosines in cellular RNAs. Aberrant interferon expression occurs in patients in whom ADAR1 mutations cause Aicardi-Goutières syndrome (AGS) or dystonia arising from striatal neurodegeneration. Adar1 mutant mouse embryos show aberrant interferon induction and die by embryonic day E12.5. We demonstrate that Adar1 embryonic lethality is rescued to live birth in Adar1; Mavs double mutants in which the antiviral interferon induction response to cytoplasmic double-stranded RNA (dsRNA) is prevented. Aberrant immune responses in Adar1 mutant mouse embryo fibroblasts are dramatically reduced by restoring the expression of editing-active cytoplasmic ADARs. We propose that inosine in cellular R...
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