title: Mutations in ADAR1 cause Aicardi-Goutières syndrome associated with a type I interferon signature.
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.
authors.affiliation: Manchester Academic Health Science Centre, University of Manchester, Genetic Medicine, UK.
authors.forename: Gillian I
authors.initials: GI
authors.lastname: Rice
authors.forename: Paul R
authors.initials: PR
authors.lastname: Kasher
authors.forename: Gabriella M A
authors.initials: GM
authors.lastname: Forte
authors.forename: Niamh M
authors.initials: NM
authors.lastname: Mannion
authors.forename: Sam M
authors.initials: SM
authors.lastname: Greenwood
authors.forename: Marcin
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authors.lastname: Szynkiewicz
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Dickerson
authors.forename: Sanjeev S
authors.initials: SS
authors.lastname: Bhaskar
authors.forename: Massimiliano
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authors.lastname: Zampini
authors.forename: Tracy A
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authors.lastname: Briggs
authors.forename: Emma M
authors.initials: EM
authors.lastname: Jenkinson
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authors.initials: CA
authors.lastname: Bacino
authors.forename: Roberta
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authors.lastname: Battini
authors.forename: Enrico
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authors.forename: Paul A
authors.initials: PA
authors.lastname: Brogan
authors.forename: Louise A
authors.initials: LA
authors.lastname: Brueton
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Carpanelli
authors.forename: Corinne
authors.initials: C
authors.lastname: De Laet
authors.forename: Pascale
authors.initials: P
authors.lastname: de Lonlay
authors.forename: Mireia
authors.initials: M
authors.lastname: del Toro
authors.forename: Isabelle
authors.initials: I
authors.lastname: Desguerre
authors.forename: Elisa
authors.initials: E
authors.lastname: Fazzi
authors.forename: Angels
authors.initials: A
authors.lastname: Garcia-Cazorla
authors.forename: Arvid
authors.initials: A
authors.lastname: Heiberg
authors.forename: Masakazu
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authors.lastname: Kawaguchi
authors.forename: Ram
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authors.lastname: Kumar
authors.forename: Jean-Pierre S-M
authors.initials: JP
authors.lastname: Lin
authors.forename: Charles M
authors.initials: CM
authors.lastname: Lourenco
authors.forename: Alison M
authors.initials: AM
authors.lastname: Male
authors.forename: Wilson
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authors.lastname: Marques
authors.forename: Cyril
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authors.lastname: Mignot
authors.forename: Ivana
authors.initials: I
authors.lastname: Olivieri
authors.forename: Simona
authors.initials: S
authors.lastname: Orcesi
authors.forename: Prab
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authors.lastname: Prabhakar
authors.forename: Magnhild
authors.initials: M
authors.lastname: Rasmussen
authors.forename: Robert A
authors.initials: RA
authors.lastname: Robinson
authors.forename: Flore
authors.initials: F
authors.lastname: Rozenberg
authors.forename: Johanna L
authors.initials: JL
authors.lastname: Schmidt
authors.forename: Katharina
authors.initials: K
authors.lastname: Steindl
authors.forename: Tiong Y
authors.initials: TY
authors.lastname: Tan
authors.forename: William G
authors.initials: WG
authors.lastname: van der Merwe
authors.forename: Adeline
authors.initials: A
authors.lastname: Vanderver
authors.forename: Grace
authors.initials: G
authors.lastname: Vassallo
authors.forename: Emma L
authors.initials: EL
authors.lastname: Wakeling
authors.forename: Evangeline
authors.initials: E
authors.lastname: Wassmer
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Whittaker
authors.forename: John H
authors.initials: JH
authors.lastname: Livingston
authors.forename: Pierre
authors.initials: P
authors.lastname: Lebon
authors.forename: Tamio
authors.initials: T
authors.lastname: Suzuki
authors.forename: Paul J
authors.initials: PJ
authors.lastname: McLaughlin
authors.forename: Liam P
authors.initials: LP
authors.lastname: Keegan
authors.forename: Mary A
authors.initials: MA
authors.lastname: O'Connell
authors.forename: Simon C
authors.initials: SC
authors.lastname: Lovell
authors.forename: Yanick J
authors.initials: YJ
authors.lastname: Crow
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics*; D020087:Alu Elements / Q000235:genetics; D000818:Animals; D020274:Autoimmune Diseases of the Nervous System / Q000235:genetics*; D059472:Exome; D015870:Gene Expression; D006801:Humans; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009154:Mutation; D009421:Nervous System Malformations / Q000235:genetics*; D011487:Protein Conformation; D012330:RNA, Double-Stranded / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins; D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D013329:Structure-Activity Relationship
chemical_list: D007370:Interferon Type I; D012330:RNA, Double-Stranded; D016601:RNA-Binding Proteins; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase