title: The role of RNA editing by ADAR1 in prevention of innate immune sensing of self-RNA.
abstract: The innate immune system is the first line of the cellular defence against invading pathogens. A critical component of this defence is the capacity to discriminate foreign RNA molecules, which are distinct from most cellular RNAs in structure and/or modifications. However, a series of rare autoimmune/autoinflammatory diseases in humans highlight the propensity for the innate immune sensing system to be activated by endogenous cellular double-stranded RNAs (dsRNAs), underscoring the fine line between distinguishing self from non-self. The RNA editing enzyme ADAR1 has recently emerged as a key regulator that prevents innate immune pathway activation, principally the cytosolic dsRNA sensor MDA5, from inducing interferon in response to double-stranded RNA structures within endogenous RNAs. Adenosine-to-Inosine RNA editing by ADAR1 is proposed to destabilise duplexes formed from inverted repetitive elements within RNAs, which appear to prevent MDA5 from sensing these RNA as virus-like in the cytoplasm. Aberrant activation of these pathways has catastrophic effects at both a cellular and organismal level, contributing to one of the causes of the conditions collectively known as the type I interferonopathies.
authors.affiliation: St. Vincent's Institute of Medical Research, 9 Princes St, Fitzroy, 3065, Victoria, Australia.
authors.forename: Jacki E
authors.initials: JE
authors.lastname: Heraud-Farlow
authors.affiliation: St. Vincent's Institute of Medical Research, 9 Princes St, Fitzroy, 3065, Victoria, Australia. cwalkley@svi.edu.au.|Department of Medicine, St. Vincent's Hospital, University of Melbourne, Fitzroy, 3065, Victoria, Australia. cwalkley@svi.edu.au.
authors.forename: Carl R
authors.initials: CR
authors.lastname: Walkley
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology; D000243:Adenosine Deaminase / Q000276:immunology*; D000818:Animals; D003593:Cytoplasm; D006801:Humans; D007113:Immunity, Innate; D000072640:Interferon-Induced Helicase, IFIH1 / Q000276:immunology; D012313:RNA / Q000276:immunology*; D017393:RNA Editing; D016601:RNA-Binding Proteins / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C505371:MAVS protein, human; D016601:RNA-Binding Proteins; D012313:RNA; C000595356:ADAR protein, human; D000243:Adenosine Deaminase; C452815:IFIH1 protein, human; D000072640:Interferon-Induced Helicase, IFIH1
keywords: ADAR1; Innate immune sensing; Interferonopathy; MDA5; RNA editing; dsRNA