Comparative analysis of the DRADA A-to-I RNA editing gene from mammals, pufferfish and zebrafish.
The DRADA gene in mammals encodes an A-to-I RNA editase, an adenosine deaminase that acts on pre-mRNAs to produce site specific inosines. DRADA has been shown to deaminate specific adenosine residues in a subset of glutamate and serotonin receptors, and this editing results in proteins of altered sequences and functional properties. DRADA thus plays a role in creating protein diversity. To study the evolutionary significance of this gene, we have characterized the genomic structure of DRADA from Fugu rubripes, and compared the protein sequences of DRADA from mammals, pufferfish and zebrafish. The DRADA gene from Fugu is three-fold compacted with respect to the human gene, and contains a novel intron within the large second coding exon. DRADA cDNAs were isolated from zebrafish and a second pufferfish, Tetraodon fluviatilis. Comparisons among fish, and between fish and mammals, of the protein sequences show that the catalytic domains are highly conserved for each gene, while the RNA binding domains vary within a single protein in their levels of conservation. Conservation within the Z DNA binding domain has also been assessed. Different levels of conservation among domains of different functional roles may reflect differences in editase substrate specificity and/or substrate sequence conservation.
Slavov
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D
Eleanor Roosevelt Institute, Denver, CO, USA.
Crnogorac-Jurcević
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Clark
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Gardiner
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K
D000243:Adenosine Deaminase / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D004247:DNA / Q000737:chemistry / Q000235:genetics; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D005091:Exons; D005399:Fishes; D005796:Genes / Q000235:genetics; D006801:Humans; D007438:Introns; D008322:Mammals; D051379:Mice; D008969:Molecular Sequence Data; D017393:RNA Editing; D016601:RNA-Binding Proteins; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D015027:Zebrafish
D018076:DNA, Complementary; D016601:RNA-Binding Proteins; D004247:DNA; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase