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Published online 15 April 2004

Nucleic Acids Research, 2004, Vol. 32, No. 7 2113-2122
© 2004 Oxford University Press

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

Rachel Flomen1, Joanne Knight2, Pak Sham1,2, Robert Kerwin1 and Andrew Makoff*,1

1 Division of Psychological Medicine and 2 Social Genetic Developmental Psychiatry Centre, Institute of Psychiatry, London SE5 7AF, UK

*To whom correspondence should be addressed. Tel: +44 207 848 0638; Fax: +44 207 848 0051; Email: a.makoff{at}iop.kcl.ac.uk

Received February 12, 2004; Revised March 8, 2004; Accepted March 22, 2004

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.


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