dADAR, a Drosophila double-stranded RNA-specific adenosine deaminase is highly developmentally regulated and is itself a target for RNA editing

SummaryAdenosine deaminases acting on RNA (ADARs) convert adenosines to inosines in double-stranded RNA in animals. Identification of more ADAR targets and genome sequences of diverse eukaryotes present an opportunity to elucidate the origin and evolution of ADAR-mediated RNA editing. Comparative analysis of the adenosine deaminase family indicates that the first ADAR might have evolved from adenosine deaminases acting on tRNAs after the split of protozoa and metazoa. ADAR1 and ADAR2 arose by gene duplications in early metazoan evolution, 700 million years ago, while ADAR3 and TENR might originate after Urochordata-Vertebrata divergence. More ADAR or ADAR-like genes emerged in some animals (e.g., fish). Considering the constrained structure, ADAR targets are proposed to have evolved from transposable elements and repeats, random selection, and fixation, and intermolecular pairs of sense and antisense RNA. In some degree, increased ADAR-mediated gene regulation should substantially contribute to the emergence and evolution of complex metazoans, particularly the nervous system.2009 IUBMB IUBMB Life, 61(6): 572-578, 2009

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“…The Drosophila genome encodes one ADAR (15), which is more similar to vertebrate ADAR2 than to ADAR1 (4) (Fig. 1).…”

Section: Origin and Evolution Of Adarmentioning

confidence: 99%

Origins and evolution of ADAR‐mediated RNA editing

2009

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“…The role of the dsRBDs in ADAR proteins is to recognize and bind to dsRNA thereby bringing the deaminase catalytic domain to its substrate adenosine at specific editing sites. Whereas two functional enzymes are present in vertebrates (ADAR1 and ADAR2), Drosophila has a single ADAR protein (dADAR) related to vertebrates ADAR2 [22,23]. The structure of mammalian ADAR2 deaminase domain [24] and ADAR2 dsRBDs have been determined in their free state [25].…”

Section: Introductionmentioning

confidence: 99%

Solution structure of the N-terminal dsRBD of Drosophila ADAR and interaction studies with RNA

2012

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Adenosine deaminases that act on RNA (ADAR) catalyze adenosine to inosine (A-to-I) editing in double-stranded RNA (dsRNA) substrates. Inosine is read as guanosine by the translation machinery; therefore A-to-I editing events in coding sequences may result in recoding genetic information. Whereas vertebrates have two catalytically active enzymes, namely ADAR1 and ADAR2, Drosophila has a single ADAR protein (dADAR) related to ADAR2. The structural determinants controlling substrate recognition and editing of a specific adenosine within dsRNA substrates are only partially understood. Here, we report the solution structure of the N-terminal dsRNA binding domain (dsRBD) of dADAR and use NMR chemical shift perturbations to identify the protein surface involved in RNA binding. Additionally, we show that Drosophila ADAR edits the R/G site in the mammalian GluR-2 pre-mRNA which is naturally modified by both ADAR1 and ADAR2. We then constructed a model showing how dADAR dsRBD1 binds to the GluR-2 R/G stem-loop. This model revealed that most side chains interacting with the RNA sugar-phosphate backbone need only small displacement to adapt for dsRNA binding and are thus ready to bind to their dsRNA target. It also predicts that dADAR dsRBD1 would bind to dsRNA with less sequence specificity than dsRBDs of ADAR2. Altogether, this study gives new insights into dsRNA substrate recognition by Drosophila ADAR.

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“…The deamination reaction is catalyzed by two different kinds of enzymes: adenosine deaminases that act on RNA (ADAR) and adenosine deaminases that act on tRNA (ADAT). ADAR specifically acts on dsRNAs [26][27][28][29][30][31], while ADAT is a tRNA-specific adenosine deaminase [32][33][34][35][36].…”

Section: A-to-i Rna Editor Genes: Adar and Adatmentioning

confidence: 99%

“…ADARs were discovered as dsRNA-specific adenosine deaminases [26][27][28][29][30][31]. They are not sequence specific; binding sites occur along the entire sequence of perfectly paired dsRNAs.…”

Section: A-to-i Rna Editor Genes: Adar and Adatmentioning

confidence: 99%

ADAR-mediated RNA editing in non-coding RNA sequences

Yang

Zhou

Jin

2013

Sci. China Life Sci.

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Adenosine to inosine (A-to-I) RNA editing is the most abundant editing event in animals. It converts adenosine to inosine in double-stranded RNA regions through the action of the adenosine deaminase acting on RNA (ADAR) proteins. Editing of pre-mRNA coding regions can alter the protein codon and increase functional diversity. However, most of the A-to-I editing sites occur in the non-coding regions of pre-mRNA or mRNA and non-coding RNAs. Untranslated regions (UTRs) and introns are located in pre-mRNA non-coding regions, thus A-to-I editing can influence gene expression by nuclear retention, degradation, alternative splicing, and translation regulation. Non-coding RNAs such as microRNA (miRNA), small interfering RNA (siRNA) and long non-coding RNA (lncRNA) are related to pre-mRNA splicing, translation, and gene regulation. A-to-I editing could therefore affect the stability, biogenesis, and target recognition of non-coding RNAs. Finally, it may influence the function of non-coding RNAs, resulting in regulation of gene expression. This review focuses on the function of ADAR-mediated RNA editing on mRNA non-coding regions (UTRs and introns) and non-coding RNAs (miRNA, siRNA, and lncRNA).

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dADAR, a Drosophila double-stranded RNA-specific adenosine deaminase is highly developmentally regulated and is itself a target for RNA editing

Cited by 175 publications

References 64 publications

Origins and evolution of ADAR‐mediated RNA editing

Origins and evolution of ADAR‐mediated RNA editing

Solution structure of the N-terminal dsRBD of Drosophila ADAR and interaction studies with RNA

ADAR-mediated RNA editing in non-coding RNA sequences

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