Molecular cloning of cDNA for double-stranded RNA adenosine deaminase, a candidate enzyme for nuclear RNA editing.

Kim, Unkyu; Wang, Yi; Sanford, Tamara; Zeng, Yong; Nishikura, Kazuko

doi:10.1073/pnas.91.24.11457

Cited by 420 publications

(418 citation statements)

References 27 publications

Supporting

Mentioning

409

Contrasting

Order By: Relevance

“…Soon after, however, it was discovered that this activity is in fact a dsRNAspecific adenosine deaminase 26,27 . The first mammalian ADAR gene, human ADAR1, was cloned following the biochemical purification and microsequencing of the ADAR1 protein 30 , which then led to the identification of ADAR2 ( ) and ADAR3 ( REFS 34,35 ) (FIG. 2a).…”

Section: Adar Genesmentioning

confidence: 99%

“…The dsRNAbinding domain (dsRBD; ∼65 amino acids) makes direct contact with the dsRNA 37 and is required for dsRNA binding. The C-terminal region of ADAR contains amino-acid residues that are conserved in several cytidine deaminases and are predicted to participate in the formation of the catalytic centre of ADAR 30,38 . The crystal structure of the catalytic domain of human ADAR2 shows that His394, Glu396 and two Cys residues, Cys451 and Cys516, of ADAR2 are indeed involved in the coordination of a zinc atom and the formation of the catalytic centre 39 .…”

Section: Domain Structure Of Adarsmentioning

confidence: 99%

“…Both ADAR1 and ADAR2 are present in many tissues, whereas ADAR3 is expressed only in the brain [30][31][32][33][34][35] . Two isoforms of ADAR1, a full-length ADAR1L and a shorter, N-terminaltruncated ADAR1S, are known 40 .…”

Section: Adar Gene Expression and Regulationmentioning

confidence: 99%

“…2a). The enzymatic activity of ADAR1 and ADAR2 has been shown [30][31][32][33] . ADAR3 activity has not yet been shown, although functional domain features are conserved in this family member 34,35 .…”

mentioning

confidence: 99%

See 3 more Smart Citations

Editor meets silencer: crosstalk between RNA editing and RNA interference

Nishikura

2006

Nat Rev Mol Cell Biol

258

263

View full text Add to dashboard Cite

The most prevalent type of RNA editing is mediated by ADAR (adenosine deaminase acting on RNA) enzymes, which convert adenosines to inosines (a process known as A→I RNA editing) in double-stranded (ds)RNA substrates. A→I RNA editing was long thought to affect only selected transcripts by altering the proteins they encode. However, genome-wide screening has revealed numerous editing sites within inverted Alu repeats in introns and untranslated regions. Also, recent evidence indicates that A→I RNA editing crosstalks with RNA-interference pathways, which, like A→I RNA editing, involve dsRNAs. A→I RNA editing therefore seems to have additional functions, including the regulation of retrotransposons and gene silencing, which adds a new urgency to the challenges of fully understanding ADAR functions.An RNA transcript is subjected to various maturation processes, such as 5′ capping, splicing, 3′ processing and polyadenylation, after it is transcribed from the gene. Post-transcriptional processing of primary transcripts is essential to generate mature messenger RNAs that are ready to be translated into proteins 1 . RNA editing is a post-transcriptional-processing mechanism that results in an RNA sequence that is different from the one encoded by the genome, and thereby contributes to the diversity of gene products. There are different types of RNA-editing mechanism that either add or delete nucleotides, or that change one nucleotide into another 2 (BOX 1).The type of RNA editing that is most prevalent in higher eukaryotes converts adenosine (A) residues into inosine (I) in double-stranded (ds)RNAs through the action of ADAR (adenosine deaminase acting on RNA) enzymes [3][4][5] . A→I RNA editing of a short dsRNA that has formed between a coding exon and nearby intron sequences can lead to a codon change and an alteration in the protein function. However, it was recently discovered that the most frequent targets of A→I RNA editing seem to be long, but partially double-stranded, RNAs that are formed from inverted Alu repeats and long interspersed element (LINE) repeats located in introns and untranslated regions (UTRs) of mRNAs [6][7][8][9] . Global editing of non-coding RNA might control the expression of genes that harbour these repeat sequences of retrotransposon origin.Post-transcriptional gene regulation can also occur through RNA interference (RNAi), an evolutionarily conserved phenomenon that involves dsRNA molecules 10,11 . Small interfering RNAs (siRNAs) and microRNAs (miRNAs) are non-coding RNAs that are generated by a class of RNase III ribonucleases (specifically, Dicer and Drosha). These small RNAs are incorporated into the RNA-induced silencing complex (RISC), which mediates the RNAi process [12][13][14][15][16] . The idea that the RNAi and A→I RNA editing pathways might compete for a Competing interests statement: The author declares no competing financial interests. [23][24][25] . NIH Public AccessIn this review, I discuss recent findings on new functions of A→I RNA editing in the regulation of non...

show abstract

Section: Adar Genesmentioning

confidence: 99%

Section: Domain Structure Of Adarsmentioning

confidence: 99%

Section: Adar Gene Expression and Regulationmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Editor meets silencer: crosstalk between RNA editing and RNA interference

Nishikura

2006

Nat Rev Mol Cell Biol

258

263

View full text Add to dashboard Cite

show abstract

“…The predicted dADAR protein is approximately the same size as the mammalian ADAR2 homologs (dADAR ϭ 670 amino acids, ratADAR2 ϭ 711 amino acids, ratRED2 ϭ 746 amino acids)+ Overall, dADAR has 43% identity to rADAR2 and 35% identity to RED2+ Within the deaminase domain, however, the homology rises to 46% identity for hADAR1 and 67% identity for hADAR2 enzymes+ Residues important for coordinating zinc in the catalytic domain are also absolutely conserved (Betts et al+, 1994;Kim et al+, 1994, Lai et al+, 1995 (Fig+ 3)+ In contrast, comparison with a tRNA-specific adenosine deaminase, dADAT1, revealed only 17% identity overall and 28% identity within the catalytic domain (Keegan et al+, 1999)+ dADAR encodes a dsRNA-specific adenosine deaminase…”

Section: Cdna Analysis Of Dadarmentioning

confidence: 99%

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

Palladino

Keegan

O’Connell

et al. 2000

RNA

176

170

View full text Add to dashboard Cite

We have identified a homolog of the ADAR (adenosine deaminases that act on RNA) class of RNA editases from Drosophila, dADAR. The dADAR locus has been localized to the 2B6-7 region of the X chromosome and the complete genomic sequence organization is reported here. dADAR is most homologous to the mammalian RNA editing enzyme ADAR2, the enzyme that specifically edits the Q/R site in the pre-mRNA encoding the glutamate receptor subunit GluR-B. Partially purified dADAR expressed in Pichia pastoris has robust nonspecific A-to-I deaminase activity on synthetic dsRNA substrates. Transcripts of the dADAR locus originate from two regulated promoters. In addition, alternative splicing generates at least four major dADAR isoforms that differ at their amino-termini as well as altering the spacing between their dsRNA binding motifs. dADAR is expressed in the developing nervous system, making it a candidate for the editase that acts on para voltage-gated Na 1 channel transcripts in the central nervous system. Surprisingly, dADAR itself undergoes developmentally regulated RNA editing that changes a conserved residue in the catalytic domain. Taken together, these findings show that both transcription and processing of dADAR transcripts are under strict developmental control and suggest that the process of RNA editing in Drosophila is dynamically regulated.

show abstract

Changing genetic information through RNA editing

2000

View full text Add to dashboard Cite

RNA editing, the post-transcriptional alteration of a gene-encoded sequence, is a widespread phenomenon in eukaryotes. As a consequence of RNA editing, functionally distinct proteins can be produced from a single gene. The molecular mechanisms involved include single or multiple base insertions or deletions as well as base substitutions. In mammals, one type of substitutional RNA editing, characterized by site-specific base-modification, was shown to modulate important physiological processes. The underlying reaction mechanism of substitutional RNA editing involves hydrolytic deamination of cytosine or adenosine bases to uracil or inosine, respectively. Protein factors have been characterized that are able to induce RNA editing in vitro. A supergene family of RNA-dependent deaminases has emerged with the recent addition of adenosine deaminases specific for tRNA. Here we review the developments that have substantially increased our understanding of base-modification RNA editing over the past few years, with an emphasis on mechanistic differences, evolutionary aspects and the first insights into the regulation of editing activity.

show abstract

Molecular cloning of cDNA for double-stranded RNA adenosine deaminase, a candidate enzyme for nuclear RNA editing.

Cited by 420 publications

References 27 publications

Editor meets silencer: crosstalk between RNA editing and RNA interference

Editor meets silencer: crosstalk between RNA editing and RNA interference

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

Changing genetic information through RNA editing

Contact Info

Product

Resources

About