RNA EDITING OF HUMAN KAINATE RECEPTOR SUBUNITS

RNA editing has been shown to be critical in generating the molecular diversity of rodent kainate receptors. We have examined cDNAs derived from various human brain sources to assess the occurrence and extent o f RNA editing in human brain. Comparison of genomic and cDNA sequences revealed extensive editing of the human EAA4 (GluR6) mRNA at the isol eucine/valine(567), tyrosine/cysteine(571) sites of the transmembrane I region, and the glutamine/arginine(621) site of the transmembrane II region. Of the eight potential molecular variants generated by the nu cleotide exchange, five were observed in the tissues examined. The dis tribution of the various RNA editing combinations were not uniform, an d displayed tissue and/or age dependent distribution. Editing of the g lutamine/arginine(621) site was also confirmed for EAA3 (GluR5), which displays a significantly higher extent of editing in specific human b rain regions compared with rodent whole brain. Hence, it can be conclu ded that RNA editing is a determinant of the phenotype of human kainat e receptor complexes.