Comparative analysis of the RED1 and RED2 A-to-I RNA editing genes from mammals, pufferfish and zebrafish

One type of RNA editing involves the deamination of adenosine (A) residues to inosines (I) at specific sites in specific pre mRNAs. These inosines are subsequently read as guanosines by the ribosome, with potentially signific ant consequences for protein sequence. In mammals, two such A-to-I RNA edit ases are RED1, which edits some serotonin and glutamate receptors, and RED2 , with unidentified substrates. To study the evolutionary conservation amon g these editases, we have isolated homologous genes from the Japanese puffe rfish, Fugu rubripes. Fugu has two genes homologous to Red1 that are simila r in size and organization and that show a fivefold compaction relative to the human gene; they differ, however, in their base compositional features. The Fugu gene for RED2 is unusually large, spanning more than 50 kb; withi n the largest intron, there is evidence for a novel gene on the opposite st rand. Because of these unusual features, the partial genomic structure was determined for the mouse RED2 gene. A partial cDNA for RED1 was also isolat ed from zebrafish. Comparisons between 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. Different levels of conservation among dom ains of different functional roles may reflect differences in editase subst rate specificity and/or substrate sequence conservation. (C) 2000 Elsevier Science B.V. All rights reserved.