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 of RNA editing in human brain. Comparison of genomic and cDNA sequences revealed extensive editing of the human EAA4 (GluR6) mRNA at the isoleucine/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 nucleotide exchange, five were observed in the tissues examined. The distribution of the various RNA editing combinations were not uniform, and displayed tissue and/or age dependent distribution. Editing of the glutamine/arginine(621) site was also confirmed for EAA3 (GluR5), which displays a significantly higher extent of editing in specific human brain regions compared with rodent whole brain. Hence, it can be concluded that RNA editing is a determinant of the phenotype of human kainate receptor complexes.