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PMID: 15087490 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

Evidence that RNA editing modulates splice site selection in the 5-HT2C receptor gene.

Nucleic acids research ·Vol. 32 ·No. 7 ·2004-00-00 ·Pages 2113-22

Flomen R, Knight J, Sham P, Kerwin R, Makoff A

Abstract

Adenosine to inosine editing of mRNA from the human 5-HT2C receptor gene (HTR2C) occurs at five exonic positions (A-E) in a stable stem-loop that includes the normal 5' splice site of intron 5 and is flanked by two alternative splice sites. Using in vitro editing, we identified a novel editing site (F) located in the intronic part of the stem-loop and demonstrated editing at this site in human brain. We have shown that in cell culture, base substitutions to mimic editing at different combinations of the six sites profoundly affect relative splicing at the normal and the upstream alternative splice site, but splicing at the downstream alternative splice site was consistently rare. Editing combinations in different splice variants from human brain were determined and are consistent with the effects of editing on splicing observed in cell culture. As RNA editing usually occurs close to exon/intron boundaries, this is likely to be a general phenomenon and suggests an important novel role for RNA editing.

MeSH Terms
Aged Aged, 80 and over Alternative Splicing/genetics Animals Base Sequence Binding Sites/genetics Brain/metabolism COS Cells Cell Line Cell Line, Tumor Female Humans Introns/genetics Male Models, Genetic Molecular Sequence Data Mutation PC12 Cells RNA/genetics,metabolism RNA Editing Rats Receptor, Serotonin, 5-HT2C/genetics
Chemicals
Receptor, Serotonin, 5-HT2C RNA
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Flomen Rachel
Division of Psychological Medicine, Institute of Psychiatry, London SE5 7AF, UK.
Knight Joanne
Sham Pak
Kerwin Robert
Makoff Andrew
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gkh536
Published
2004-00-00
Epub
2004-00-15
Pages
2113-22
Language
English
Region
England
NLM ID
0411011
PMCID
PMC407821
Subset
IM
External Links
PubMed source DOI: 10.1093/nar/gkh536 PMC Full Text View journal details
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