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

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 ma mmalian RNA editing enzyme ADAR2, the enzyme that specifically edits the Q/ R site in the pre-mRNA encoding the glutamate receptor subunit GluR-B. Part ially purified dADAR expressed in Pichia pastoris has robust nonspecific A- to-I deaminase activity on synthetic dsRNA substrates. Transcripts of the d ADAR 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 ca ndidate for the editase that acts on para voltage-gated Naf channel transcr ipts in the central nervous system. Surprisingly, dADAR itself undergoes de velopmentally regulated RNA editing that changes a conserved residue in the catalytic domain. Taken together, these findings show that both transcript ion and processing of dADAR transcripts are under strict developmental cont rol and suggest that the process of RNA editing in Drosophila is dynamicall y regulated.