A-to-I pre-mRNA editing of the serotonin 2C receptor

The serotonin receptor 5HT2cR, which is a G-protein coupled receptor in the central nervous system, is subject to adenosine to inosine (A-to-I) RNA editing at five residues. Such modifications affect the genomically encoded amino acids I, N and I at positions 157, 159 and 161, and produce up to 32 mRNA variants, encoding 24 protein isoforms, some of which vary in biochemical and pharmacological properties.; Because serotonin mediates neurological processes relevant to behavior and because inbred mouse strains vary in their responses to tests of learning and behavior, we have examined the editing patterns of the 5HT2CR mRNA in whole brains from eight mouse strains. By sequencing approximately 100 clones from individual mice, we observed significant differences in the frequency of editing at the A, B, E and D sites, in the proportion of transcripts with 1 and 4 edited sites, and in the frequency of RNA encoding V at positions 157 and 161, the INV and VSI isoforms, the less active group of VNV/VSV and the more active group of INV/VSI/ISV in subsets of pairwise comparisons. Primer extension assays showed that individuals within strains (C3H.B-+rd1 and 129SvImrJ) displayed no significant differences. These findings suggest that genetic background contributes to subtle variation in 5HT2CR mRNA editing patterns.; Because exposure to the Morris Water Maze was reported to cause time-dependent changes in the level of 5HT2cR mRNA, we tested if it also caused alterations in the editing patterns. We used primer extension assays to compare editing patterns in whole brains from Water Maze-trained mice, swimming controls and naive controls at 1 h, 6 h and 24 h after swimming. Time-dependent changes in levels of editing at the B, E and D sites and in levels of RNA encoding SI/GI or NV/GV at 159 and 161 were found between Water Maze-trained mice and naive controls. We also examined editing patterns in hippocampus and cortex. Independent of treatment or time, differences were found in hippocampus and cortex of subsets of mice, especially at the A and B sites. These results suggest interactions of treatment, time and brain regions.