RNA editing modulates the transcriptional repression activity of CtBP1

Abstract

RNA modification includes alternative splicing and RNA editing, which increases the diversity of transcripts and proteins. The C-terminal binding protein (CtBP), a transcriptional corepressor, has alternative splicing forms but there is no information about involving RNA editing in CtBP function. Here we found a unique transcript variant of CtBP1 with an A-to-G conversion at codon 528 in breast cancer cell lines. CtBP1 mRNA editing produces protein in which threonine-176 is changed into alanine. This CtBP1 (T176A) mutant lacks in vitro dehydrogenase activity and dimerization ability compared with wild-type CtBP1. Microarray analysis showed that many oncogenes were upregulated in CtBP-knockout mouse embryonic fibroblast. These candidate target genes were repressed by restoring wild-type CtBP1, but not by CtBP1 (T176A) mutant, indicating that CtBP1 (T176A) mutant is defective in transcriptional repression activity. We propose that RNA editing modulates the role of CtBP1 in transcription repression of oncogenes involved in breast cancer cells.