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 cation flow in alpha-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 regulated. Sequence analysis of human genomic DNA revealed a Q codon (CAG) in the putative channel-forming segment of human GluR-2, whereas in the majority of cDNA clones an R codon (CGG) was found. Examination of editing in various brain tissues revealed differences in the efficiency of this process. The hippocampus, cerebellum and temporal cortex harbour 100% edited GluR-2, whereas only 72% of substantia nigra, 89% of corpus striatum and 96% of fetal cDNAs have been found to be edited. This new discovery of differential efficiency of RNA editing has important implications in AMPA receptor channel-mediated calcium influx. AMPA receptors are thought to mediate the majority of the fast excitatory synaptic 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 and could be related to certain neurodegenerative diseases.
Nutt
S L
SL
Allelix Biopharmaceuticals Inc., Mississauga, Ontario, Canada.
Kamboj
R K
RK
D000818:Animals; D001483:Base Sequence; D001923:Brain Chemistry / Q000502:physiology*; D003062:Codon; D004247:DNA / Q000032:analysis; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D017393:RNA Editing / Q000502:physiology*; D018091:Receptors, AMPA / Q000096:biosynthesis*
D003062:Codon; D007473:Ion Channels; D018091:Receptors, AMPA; D004247:DNA