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+ 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.