Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
TY - JOUR
T1 - Evidence that RNA editing modulates splice site selection in the 5-HT2C receptor gene
AU - Flomen, Rachel
AU - Knight, Joanne
AU - Sham, Pak
AU - Kerwin, Robert
AU - Makoff, Andrew
PY - 2004/4/1
Y1 - 2004/4/1
N2 - 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.
AB - 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.
KW - Aged
KW - Aged, 80 and over
KW - Alternative Splicing
KW - Animals
KW - Base Sequence
KW - Binding Sites
KW - Brain
KW - COS Cells
KW - Cell Line
KW - Cell Line, Tumor
KW - Female
KW - Humans
KW - Introns
KW - Male
KW - Models, Genetic
KW - Molecular Sequence Data
KW - Mutation
KW - PC12 Cells
KW - RNA
KW - RNA Editing
KW - Rats
KW - Receptor, Serotonin, 5-HT2C
U2 - 10.1093/nar/gkh536
DO - 10.1093/nar/gkh536
M3 - Journal article
C2 - 15087490
VL - 32
SP - 2113
EP - 2122
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 0305-1048
IS - 7
ER -