RNA editing, well-documented in Trypanosoma brucei, provides a mechanism whereby posttranscriptional modification of RNA increases the number of protein variants coded by one gene. Now, Price et al. have found that RNA editing, which also occurs in the serotonin (5-HT) type 2c receptor (5-HT2c) in humans, can specify which G protein α subunits bind to 5-HT2c receptors. The authors compared the unedited INI isoform and the VSV and VGV edited isoforms (named for the different amino acids that arise from editing) of the 5-HT2c receptor and observed that the INI isoform bound to Gq, G13, and G15 α subunits. In contrast, Gq and G11 associated with VSV and only Gq associated with VGV. Also, stimulation of NIH 3T3 cells that expressed G13 and INI (but not cells expressing G13 and VGV), resulted in cytoskeletal rearrangements (a known G13-mediated effect), suggesting that functional interactions had occurred between G13 and INI. Thus, the data indicate that editing of receptor mRNAs can lead to specific changes in protein partners and subsequently transduced signals.
R. D. Price, D. M. Weiner, M. S. S. Chang, E. Sanders-Bush, RNA editing of the human serotonin 5-HT2c receptor alters receptor-mediated activation of G13 protein. J. Biol. Chem. 276, 44663-44668 (2001). [Abstract] [Full Text]