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Genes 2016, 7(12), 129; doi:10.3390/genes7120129

Functions of the RNA Editing Enzyme ADAR1 and Their Relevance to Human Diseases

The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA
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Academic Editor: H. Ulrich Göringer
Received: 14 October 2016 / Revised: 7 December 2016 / Accepted: 12 December 2016 / Published: 17 December 2016
(This article belongs to the Special Issue RNA Editing)
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Abstract

Adenosine deaminases acting on RNA (ADARs) convert adenosine to inosine in double-stranded RNA (dsRNA). Among the three types of mammalian ADARs, ADAR1 has long been recognized as an essential enzyme for normal development. The interferon-inducible ADAR1p150 is involved in immune responses to both exogenous and endogenous triggers, whereas the functions of the constitutively expressed ADAR1p110 are variable. Recent findings that ADAR1 is involved in the recognition of self versus non-self dsRNA provide potential explanations for its links to hematopoiesis, type I interferonopathies, and viral infections. Editing in both coding and noncoding sequences results in diseases ranging from cancers to neurological abnormalities. Furthermore, editing of noncoding sequences, like microRNAs, can regulate protein expression, while editing of Alu sequences can affect translational efficiency and editing of proximal sequences. Novel identifications of long noncoding RNA and retrotransposons as editing targets further expand the effects of A-to-I editing. Besides editing, ADAR1 also interacts with other dsRNA-binding proteins in editing-independent manners. Elucidating the disease-specific patterns of editing and/or ADAR1 expression may be useful in making diagnoses and prognoses. In this review, we relate the mechanisms of ADAR1′s actions to its pathological implications, and suggest possible mechanisms for the unexplained associations between ADAR1 and human diseases. View Full-Text
Keywords: ADAR1; RNA editing; human diseases; innate immunity ADAR1; RNA editing; human diseases; innate immunity
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Song, C.; Sakurai, M.; Shiromoto, Y.; Nishikura, K. Functions of the RNA Editing Enzyme ADAR1 and Their Relevance to Human Diseases. Genes 2016, 7, 129.

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