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The role of RNA editing by ADAR1 in prevention of innate immune sensing of self-RNA
Heraud-Farlow, Jacki E. Walkley, Carl R.
Heraud-Farlow, Jacki E.
Walkley, Carl R.
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.
Keywords
ADAR1, RNAediting, nterferonopathy, nnate immune, ensing, MDA5, sRNA
Date
2016
Type
Journal article
Journal
Journal of Molecular Medicine
Book
Volume
94
Issue
10
Page Range
1095-1102
Article Number
ACU Department
Mary MacKillop Institute for Health Research
Faculty of Health Sciences
Faculty of Health Sciences
Collections
Relation URI
Source URL
Event URL
Open Access Status
License
File Access
Controlled