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

Author

Listed:
  • Colleen M. Burns

    (Vanderbilt University School of Medicine)

  • Hsin Chu

    (Vanderbilt University School of Medicine)

  • Susan M. Rueter

    (Vanderbilt University School of Medicine)

  • Linda K. Hutchinson

    (Vanderbilt University School of Medicine)

  • Hervé Canton

    (Vanderbilt University School of Medicine)

  • Elaine Sanders-Bush

    (Vanderbilt University School of Medicine)

  • Ronald B. Emeson

    (Vanderbilt University School of Medicine)

Abstract

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-HT2B and 5-HT2C) which are linked to phospholipase C, promoting the hydrolysis of membrane phospholipids and a subsequent increase in the intracellular levels of inositol phosphates and diacylglycerol1. Here we show that transcripts encoding the 2C subtype of serotonin receptor (5-HT2CR) 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-HT2C receptor iso-forms encoded by eleven distinct RNA species. Editing of 5-HT2CR 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.

Suggested Citation

  • Colleen M. Burns & Hsin Chu & Susan M. Rueter & Linda K. Hutchinson & Hervé Canton & Elaine Sanders-Bush & Ronald B. Emeson, 1997. "Regulation of serotonin-2C receptor G-protein coupling by RNA editing," Nature, Nature, vol. 387(6630), pages 303-308, May.
  • Handle: RePEc:nat:nature:v:387:y:1997:i:6630:d:10.1038_387303a0
    DOI: 10.1038/387303a0
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    Cited by:

    1. Gaia Rizzo & Mattia Veronese & Paul Expert & Federico E Turkheimer & Alessandra Bertoldo, 2016. "MENGA: A New Comprehensive Tool for the Integration of Neuroimaging Data and the Allen Human Brain Transcriptome Atlas," PLOS ONE, Public Library of Science, vol. 11(2), pages 1-20, February.
    2. Suba Rajendren & Xiang Ye & William Dunker & Antiana Richardson & John Karijolich, 2023. "The cellular and KSHV A-to-I RNA editome in primary effusion lymphoma and its role in the viral lifecycle," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Liran Carmel & Eugene V Koonin & Stella Dracheva, 2012. "Dependencies among Editing Sites in Serotonin 2C Receptor mRNA," PLOS Computational Biology, Public Library of Science, vol. 8(9), pages 1-13, September.
    4. Marlon S. Zambrano-Mila & Monika Witzenberger & Zohar Rosenwasser & Anna Uzonyi & Ronit Nir & Shay Ben-Aroya & Erez Y. Levanon & Schraga Schwartz, 2023. "Dissecting the basis for differential substrate specificity of ADAR1 and ADAR2," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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