An Intronic Splicing Silencer Causes Skipping of the IIIb Exon of Fibroblast Growth Factor Receptor 2 through Involvement of Polypyrimidine Tract Binding Protein

摘要: Alternative splicing of fibroblast growth factor receptor 2 (FGF-R2) transcripts involves the mutually exclusive usage exons IIIb and IIIc to produce two different isoforms. Appropriate exon in rat prostate cancer DT3 cells requires a previously described cis element (ISAR, for “intronic activator repressor”) which represses activates IIIb. This is nonfunctional AT3 cells, repress inclusion splice IIIc. We have now identified an intronic upstream that causes repression splicing. Deletion this abrogates requirement ISAR order be spliced inappropriate cells. consists silencer (ISS) sequences, ISS1 ISS2. The sequence pyrimidine rich, vitro cross-linking studies demonstrate binding polypyrimidine tract protein (PTB) element. Competition mutations within abolish PTB alleviate vivo. Cotransfection PTB-1 expression vector with minigene containing PTB-mediated Furthermore, all isoforms were equally capable mediating effect. Our results support model regulation does not represent default pathway but rather one active occurs both are able overcome