DIFFERENTIAL RNA EDITING EFFICIENCY OF AMPA RECEPTOR SUBUNIT GLUR-2 IN HUMAN BRAIN

RNA editing in rat brain has been found to control a determinant of ca tion flow in lpha-amino-3-hydroxy-5-methyl-4-isoxasolepropionic acid ( AMPA)-gated channels. Here we provide the first evidence that this RNA editing phenomenon occurs in human brain and is differentially regula ted. Sequence analysis of human genomic DNA revealed a Q codon (CAG) i n the putative channel-forming segment of human GluR-2, whereas in the majority of cDNA clones an R codon (CGG) was found. Examination of ed iting in various brain tissues revealed differences in the efficiency of this process. The hippocampus, cerebellum and temporal cortex harbo ur 100% edited GluR-2, whereas only 72% of substantia nigra, 89% of co rpus striatum and 96% of fetal cDNAs have been found to be edited. Thi s new discovery of differential efficiency of RNA editing has importan t implications in AMPA receptor channel-mediated calcium influx. AMPA receptors are thought to mediate the majority of the fast excitatory s ynaptic neurotransmission; the RNA editing process may therefore play a critical role in normal brain function and development. Dysfunction of this RNA editing process may have neuropathological consequences an d could be related to certain neurodegenerative diseases.