CHARACTERIZATION OF RNA EDITING OF THE GLUTAMATE-RECEPTOR SUBUNITS GLUR5 AND GLUR6 IN GRANULE CELLS DURING CEREBELLAR DEVELOPMENT

The non-NMDA class of ionotropic glutamate receptors are subject to RN A editing resulting in single amino acid changes within individual sub units that make up these oligomeric receptors. These amino acid change s result in significant alterations of important channel properties. B oth edited and unedited versions of the kainate-receptor subunits GluR 5 and GluR6 are present in brain, but whether this reflects the expres sion of both versions in individual types of neurons or differences in editing between different cell types is unclear. To characterize edit ing in a single identified type of central neuron, we have determined the extent to which GluR5 and GluR6 mRNAs are edited in acutely isolat ed cerebellar granule cells. RT-PCR analysis revealed that editing at each site in GluR5 and GluR6 increased during early postnatal developm ent. The Q/R site was predominantly unedited in GluR5, whereas GluR6 w as mostly edited. The Q/R and Y/C sites of GluR6 were edited to simila r extents, whereas a smaller percentage of transcripts were edited at the I/V site. The expression of two double-stranded RNA adenosine deam inases implicated in GluR editing (DRADA and RED1) increased in granul e cells between postnatal days 1 and 15. Finally, cerebellar granule c ells express a previously unreported variant of RED1 which appears to arise from developmentally regulated alternative splicing. (C) 1997 El sevier Science B.V.