Identification and Characterization of RNA Editing Events within the 5-HT2C Receptora

Authors


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    This work was supported by grants from the NIH and a generous fellowship from the Pharmaceutical Manufacturers Association Foundation (CMN).

Corresponding author: Department of Pharmacology, University of Washington, Box 357750, Seattle, WA 98195-7750; Tel: 206.685.8742; Fax: 206.616.4230; http://cniswend@u.washington.edu

Abstract

ABSTRACT: RNA editing is a post-transcriptional modification that generates an RNA transcript with a nucleotide sequence different from its gene. We have recently discovered RNA editing events, involving the conversion of adenosine bases to inosine residues, within the RNA encoding the serotonin 2C (5-HT2C) receptor. 1 Editing events at four major positions, termed A, B, C and D, as well as one minor site termed C′, are predicted to alter amino acids within the second intracellular loop of the G-protein coupled 5-HT2C receptor. Editing is mediated by at least two members of a family of adenosine deaminases and is contingent upon the presence of an extensive RNA duplex structure formed by exonic and intronic sequences of 5-HT2C receptor precursor messenger RNA (pre-mRNA). This critical secondary structure has been observed within brain pre-mRNA derived from four species; the isolation of edited 5-HT2C receptor transcripts from these samples further confirms the evolutionary conservation of this RNA processing event. Among members of the 5-HT2 receptor family, editing within second intracellular loop RNA is unique to the 5-HT2C receptor. Editing within the 5-HT2C receptor generates receptor isoforms that differ in their ability to interact with the phospholipase C signaling cascade in a transfected cell line, suggesting that this RNA processing event may contribute to the modulation of serotonergic neurotransmission in the central nervous system.

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