Mutations in ADAR1 cause Aicardi-Goutières syndrome associated with a type I interferon signature

Rice, G. I. et al. (2012) Mutations in ADAR1 cause Aicardi-Goutières syndrome associated with a type I interferon signature. Nature Genetics, 44(11), pp. 1243-1248. (doi: 10.1038/ng.2414) (PMID:23001123) (PMCID:PMC4154508)

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.

• Item Type: Articles (Letter)
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Mannion, Dr Niamh and Dickerson, Dr Jonathan
• Authors: Rice, G. I., Kasher, P. R., Forte, G. M.A., Mannion, N. M., Greenwood, S. M., Szynkiewicz, M., Dickerson, J. E., Bhaskar, S. S., Zampini, M., Briggs, T. A., Jenkinson, E. M., Bacino, C. A., Battini, R., Bertini, E., Brogan, P. A., Brueton, L. A., Carpanelli, M., De Laet, C., de Lonlay, P., del Toro, M., Desguerre, I., Fazzi, E., Garcia-Cazorla, A., Heiberg, A., Kawaguchi, M., Kumar, R., Lin, J.-P. S.-M., Lourenco, C. M., Male, A. M., Marques, W., Mignot, C., Olivieri, I., Orcesi, S., Prabhakar, P., Rasmussen, M., Robinson, R. A., Rozenberg, F., Schmidt, J. L., Steindl, K., Tan, T. Y., van der Merwe, W. G., Vanderver, A., Vassallo, G., Wakeling, E. L., Wassmer, E., Whittaker, E., Livingston, J. H., Lebon, P., Suzuki, T., McLaughlin, P. J., Keegan, L. P., O'Connell, M. A., Lovell, S. C., and Crow, Y. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Nature Genetics
• Publisher: Nature Publishing Group
• ISSN: 1061-4036
• ISSN (Online): 1546-1718
• Published Online: 23 September 2012