Identification of putative dADAR substrates using full-length cDNA and EST sequence data. M. Stapleton ¹, J. Carlson ¹, S.E. Celniker ¹, G.M. Rubin ². 1) Berkeley Drosophila Genome Project and Genome Sciences Department, Lawrence Berkeley National Labs, Berkeley, CA; 2) Department of Molecular and Cell Biology, University of California, Berkeley CA, and Howard Hughes Medical Institute, University of California, Berkeley CA.

   RNA editing is a well-documented mechanism of generating nucleotide diversity beyond that directly encoded by the genome. Adenosine deaminase (ADAR) targets double-stranded regions of nuclear-encoded RNAs, catalyzing the deamination of adenosine to inosine. Inosine mimics guanosine in its base pairing properties, and the translational machinery of the cell interprets I as G. In this way, an A-to-I conversion in the mRNA can alter the genetic information and, consequently, protein function. Null mutations in the single ADAR gene in Drosophila (dADAR) suggest that the function of pre-mRNA editing is to modify adult behavior by altering signaling components in the nervous system. Among the mRNAs known to be edited in Drosophila are those encoded by cacophony (a calcium channel), paralytic (a sodium channel) and GluCla (a chloride channel), all of which have multiple editing sites in their coding sequences. In the course of evaluating the quality of the DGC full-length cDNAs, we compared their translation products to those of the recently completed Release 3 genomic sequence. Such comparisons should reveal cases of RNA editing. In cases in which the predicted protein sequences disagreed, we examined the corresponding nucleotide sequences in search of site-specific A-to-G variation between cDNA and genomic sequences. We identified over 30 candidates consistent with RNA editing; however, additional cDNA or EST data will be required to distinguish RNA editing from reverse transcriptase errors or strain polymorphisms. In a few cases we had enough cDNA and EST data to indicate that RNA editing is the most likely explanation for the observed variation. These putative new targets of pre-mRNA editing will be presented.