Regulation of serotonin 2C receptor pre-mRNA editing by serotonin

The primary transcript of the gene encoding the 5-hydroxytryptamine 2C (5-HT2C; serotonin 2C) receptor is modulated by RNA editing. In this post-transcriptional process, five closely spaced adenosines, located within a sequence encoding the second intracellular loop of the seven-transmembrane-spanning G protein-coupled receptor, are converted to inosine to alter the coding potential of three triplet codons. Theoretically, 32 5-HT2C messenger RNA (mRNA) isoforms could result from this editing, and they would encode 24 different receptor isoforms. Results of pharmacological studies have demonstrated that 5-HT2C pre-mRNA editing modulates signaling at central serotonergic synapses and that the magnitude of this modulation depends on the extent of editing and on distinct editing-site preferences. Moreover, 5-HT2C pre-mRNA editing is regulated by the cognate neurotransmitter serotonin (i.e., 5-HT). Interestingly, results of human postmortem studies indicate altered editing-site preferences in brains of suicide victims with a history of major depression that lead to increased expression of 5-HT2C mRNA isoforms encoding receptors with compromised functional properties. In this chapter, these findings are discussed within the context of the normal serotonin-dependent regulation of 5-HT2C pre-mRNA editing. © 2005 Elsevier Inc. All rights reserved.