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

Nature. 1997 May 15;387(6630):303-8. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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


  • RNA, Messenger
  • RNA-Binding Proteins
  • Receptor, Serotonin, 5-HT2C
  • Receptors, Serotonin
  • Serotonin
  • Inosine
  • ADARB1 protein, human
  • Adenosine Deaminase
  • GTP-Binding Proteins
  • Adenosine