Title |
Mutations in ADAR1 cause Aicardi-Goutières syndrome associated with a type I interferon signature
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Published in |
Nature Genetics, September 2012
|
DOI | 10.1038/ng.2414 |
Pubmed ID | |
Authors |
Gillian I Rice, Paul R Kasher, Gabriella M A Forte, Niamh M Mannion, Sam M Greenwood, Marcin Szynkiewicz, Jonathan E Dickerson, Sanjeev S Bhaskar, Massimiliano Zampini, Tracy A Briggs, Emma M Jenkinson, Carlos A Bacino, Roberta Battini, Enrico Bertini, Paul A Brogan, Louise A Brueton, Marialuisa Carpanelli, Corinne De Laet, Pascale de Lonlay, Mireia del Toro, Isabelle Desguerre, Elisa Fazzi, Àngels Garcia-Cazorla, Arvid Heiberg, Masakazu Kawaguchi, Ram Kumar, Jean-Pierre S-M Lin, Charles M Lourenco, Alison M Male, Wilson Marques, Cyril Mignot, Ivana Olivieri, Simona Orcesi, Prab Prabhakar, Magnhild Rasmussen, Robert A Robinson, Flore Rozenberg, Johanna L Schmidt, Katharina Steindl, Tiong Y Tan, William G van der Merwe, Adeline Vanderver, Grace Vassallo, Emma L Wakeling, Evangeline Wassmer, Elizabeth Whittaker, John H Livingston, Pierre Lebon, Tamio Suzuki, Paul J McLaughlin, Liam P Keegan, Mary A O'Connell, Simon C Lovell, Yanick J Crow |
Abstract |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Unknown | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Scientists | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 3 | <1% |
Chile | 1 | <1% |
Austria | 1 | <1% |
France | 1 | <1% |
Japan | 1 | <1% |
China | 1 | <1% |
Unknown | 495 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 105 | 21% |
Researcher | 89 | 18% |
Student > Master | 42 | 8% |
Student > Bachelor | 40 | 8% |
Student > Doctoral Student | 23 | 5% |
Other | 79 | 16% |
Unknown | 125 | 25% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 112 | 22% |
Biochemistry, Genetics and Molecular Biology | 110 | 22% |
Medicine and Dentistry | 66 | 13% |
Immunology and Microbiology | 31 | 6% |
Neuroscience | 17 | 3% |
Other | 28 | 6% |
Unknown | 139 | 28% |