An RNA editor, adenosine deaminase acting on double-stranded RNA (ADAR1) - PubMed (original) (raw)

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An RNA editor, adenosine deaminase acting on double-stranded RNA (ADAR1)

Cyril X George et al. J Interferon Cytokine Res. 2014 Jun.

Abstract

Adenosine deaminase acting on RNA1 (ADAR1) catalyzes the C6 deamination of adenosine (A) to produce inosine (I) in regions of RNA with double-stranded (ds) character. This process is known as A-to-I RNA editing. Alternative promoters drive the expression of the Adar1 gene and alternative splicing gives rise to transcripts that encode 2 ADAR1 protein size isoforms. ADAR1 p150 is an interferon (IFN)-inducible dsRNA adenosine deaminase found in the cytoplasm and nucleus, whereas ADAR1 p110 is constitutively expressed and nuclear in localization. Dependent on the duplex structure of the dsRNA substrate, deamination of adenosine by ADAR can be either highly site-selective or nonspecific. A-to-I editing can alter the stability of RNA structures and the coding of RNA as I is read as G instead of A by ribosomes during mRNA translation and by polymerases during RNA replication. A-to-I editing is of broad physiologic significance. Both the production and the action of IFNs, and hence the subsequent interaction of viruses with their hosts, are among the processes affected by A-to-I editing.

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Figures

**FIG. 1.

Domain organization and reaction catalyzed by adenosine deaminase acting on RNA1 (ADAR1). (A) Domain organization of human ADAR1. Alternative promoters and alternative splicing generate 2 size-isoforms of ADAR1, an interferon (IFN)-inducible p150 protein and a constitutively expressed p110 protein. The 2 Z-DNA binding domains (Zα, Zβ), the 3 double-stranded RNA (dsRNA) binding domains (RI, RII, and RIII), and the deaminase catalytic domain are shown. Alternative exon 1 and exon 7 structures give rise to the 1,200 amino acid p150 protein and 931 aa p110 protein in human cells. (B) Both p150 and p110 ADAR1 catalyze the hydrolytic C6 deamination of adenosine (A) to yield inosine (I) in dsRNA. Adapted from George and others (2011).

**FIG. 2.

A-to-I RNA editing affects multiple biochemical processes, thereby altering gene expression and function. Because I base pairs as G instead of A, nucleotide substitution of an A with an I may affect mRNA translation by altering a codon potentially leading to an amino acid substitution; RNA structure-dependent activities that trigger IFN responses may be suppressed if dsRNA structures are destabilized; the pre-mRNA splicing pattern of an RNA may be altered by editing a conserved A involved in splice site selection; RNA silencing may be altered by affecting dsRNA structures involved in either micro RNA processing or targeting; RNA virus genome stability may be altered by changing template and therefore complementary product sequences during viral RNA synthesis leading to A-to-G (U-to-C) transitions; and, A-to-I editing of noncoding repetitive (Alu) or nonrepetitive RNA elements may potentially affect RNA stability by altering cellular localization or nuclease recognition. Adapted from Samuel (2011).

References

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An RNA editor, adenosine deaminase acting on double-stranded RNA (ADAR1) - PubMed (original) (raw)