Mutations in ADAR1 cause Aicardi-Goutières syndrome associated with a type I interferon signature
By G. Rice, P. Kasher, G. Forte, Niamh M. Mannion, Sam M Greenwood, M. Szynkiewicz, Jonathan E. Dickerson, S. Bhaskar, M. Zampini, T. Briggs and 44 more. Nature Genetics, 2012
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Adenosine deaminases acting on RNA (ADARs) catalyze the hydrolytic deamination of adenosine to inosine in double-stranded RNA (dsRNA) and thereby potentially alter the information content and structure of cellular RNAs. Notably, although the overwhelming majority of such editing events occur in transcripts derived from Alu repeat elements, the biological function of non-coding RNA editing remains uncertain. Here, we show that mutations in ADAR1 (also known as ADAR) cause the autoimmune disorder Aicardi-Goutières syndrome (AGS). As in Adar1-null mice, the human disease state is associated with upregulation of interferon-stimulated genes, indicating a possible role for ADAR1 as a suppressor of type I interferon signaling. Considering recent insights derived from the study of other AGS-related proteins, we speculate that ADAR1 may limit the cytoplasmic accumulation of the dsRNA generated from genomic repetitive elements.
Subfields: Immunology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/a34f563300adec7bf9bacc75d821ed7ca61f72e8
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In Molecular Biology
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Citations in the corpus
- A census of human RNA-binding proteins (2014, background): “Immunologica l/ skin disease ADAD1, ADAD2, ADAT, ADAR, ADARB1, ADARB2 Aicardi-Goutieres syndrome (AGS), dyschromatosis symmetrica hereditaria 1 (DSH1) missense, nonsense mutation (Miyamura et al., 2003; Rice et al., 2012)”
- ADAR1 Limits RIG-I RNA Detection and Suppresses IFN Production Responding to Viral and Endogenous RNAs (2014, background): “A subset of AGS was recently found to be associated with gene mutations in adenosine deaminase acting on RNA 1 (ADAR1) loci (5).”