Regulation of serotonin-2C receptor G-protein coupling by RNA editing.

Burns CM, Chu H, Rueter SM, Hutchinson LK, Canton H, Sanders-Bush E, Emeson RB
Nature. 1997 387 (6630): 303-8

PMID: 9153397 · DOI:10.1038/387303a0

The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) elicits a wide array of physiological effects by binding to several receptor subtypes. The 5-HT2 family of receptors belongs to a large group of seven-transmembrane-spanning G-protein-coupled receptors and includes three receptor subtypes (5-HT2A, 5-HT(2B) and 5-HT(2C)) which are linked to phospholipase C, promoting the hydrolysis of membrane phospholipids and a subsequent increase in the intracellular levels of inositol phosphates and diacylglycerol. Here we show that transcripts encoding the 2C subtype of serotonin receptor (5-HT(2C)R) undergo RNA editing events in which genomically encoded adenosine residues are converted to inosines by the action of double-stranded RNA adenosine deaminase(s). Sequence analysis of complementary DNA isolates from dissected brain regions have indicated the tissue-specific expression of seven major 5-HT(2C) receptor isoforms encoded by eleven distinct RNA species. Editing of 5-HT(2C)R messenger RNAs alters the amino-acid coding potential of the predicted second intracellular loop of the receptor and can lead to a 10-15-fold reduction in the efficacy of the interaction between receptors and their G proteins. These observations indicate that RNA editing is a new mechanism for regulating serotonergic signal transduction and suggest that this post-transcriptional modification may be critical for modulating the different cellular functions that are mediated by other members of the G-protein-coupled receptor superfamily.

MeSH Terms (24)

3T3 Cells Adenosine Adenosine Deaminase Animals Binding, Competitive Brain Cell Line Choroid Plexus Corpus Striatum GTP-Binding Proteins Hippocampus Humans Inosine Mice Rats Receptor, Serotonin, 5-HT2C Receptors, Serotonin RNA, Messenger RNA-Binding Proteins RNA Editing Serotonin Signal Transduction Transfection Tumor Cells, Cultured

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