Evidence that RNA editing modulates splice site selection in the 5-HT2C receptor gene
Autor: | Joanne Knight, Andrew Makoff, Pak C. Sham, Rachel H Flomen, Robert Kerwin |
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Rok vydání: | 2004 |
Předmět: |
Male
Molecular Sequence Data Biology PC12 Cells Cell Line Exon Cell Line Tumor Receptor Serotonin 5-HT2C Genetics Animals Humans splice Gene Aged Aged 80 and over Binding Sites Splice site mutation Base Sequence Models Genetic Alternative splicing Intron Brain Articles Introns Rats Alternative Splicing RNA editing COS Cells Mutation RNA splicing RNA Female RNA Editing |
Zdroj: | Nucleic Acids Research. 32:2113-2122 |
ISSN: | 1362-4962 |
DOI: | 10.1093/nar/gkh536 |
Popis: | 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. |
Databáze: | OpenAIRE |
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