EDITING OF GLUTAMATE-RECEPTOR-B SUBUNIT ION-CHANNEL RNAS BY 4 ALTERNATIVELY SPLICED DRADA2 DOUBLE-STRANDED-RNA ADENOSINE DEAMINASES

Double-stranded (ds) RNA-specific adenosine deaminase converts adenosi ne residues into inosines in dsRNA and edits transcripts of certain ce llular and viral genes such as glutamate receptor (GluR) subunits and hepatitis delta antigen. The first member of this type of deaminase, D RADA1, has been recently cloned based on the amino acid sequence infor mation derived from biochemically purified proteins, Our search for DR ADA1-like genes through expressed sequence tag databases led to the cl oning of the second member of this class of enzyme, DRADA2, which has a high degree of sequence homology to DRADA1 get exhibits a distinctiv e RNA editing site selectivity, There are four differentially spliced isoforms of human DRADA2. These different isoforms of recombinant DRAD A2 proteins, including one which is a human homolog of the recently re ported rat RED1, were analyzed in vitro for their GluR B subunit (GluR -B) RNA editing site selectivity, As originally reported for rat RED1, the DRADA2a and 2b isoforms edit GluR-B RNA efficiently at the so-cal led Q/R site, whereas DRADA1 barely edits this site. In contrast, the R/G site of GluR-B RNA was edited efficiently by the DRADA2a and -2b i soforms as well as DRADA1, Isoforms DRADA2c and -2d, which have a dist inctive truncated shorter C-terminal structure, displayed weak adenosi ne-to-inosine conversion activity but no editing activity tested at th ree known sites of GluR-B RNA. The possible role of these DRADA2c and -2d isoforms in the regulatory mechanism of RNA editing is discussed.