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

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 ToroIsabelle 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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1243-1248
Number of pages6
JournalNature Genetics
Volume44
Issue number11
DOIs
Publication statusPublished - Nov 2012

ASJC Scopus subject areas

  • Genetics

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