Polypyrimidine tract-binding protein down-regulates fibroblast growth factor receptor 1 α-exon inclusion

Exclusion of the α-exon by alternative RNA splicing of the fibroblast growth factor receptor 1 (FGFR1) primary transcript leads to the production of FGFR1β. Glial cell transformation is associated with a progressive increase in FGFR1β expression that coincides with a dramatic increase in the expression of the splicing factor polypyrimidine tract-binding protein (PTB). Cell-specific overexpression of PTB increased α-exon skipping, and a reduction in PTB increased α-exon inclusion. Targeted disruption of PTB interaction with FGFR1 precursor RNA in vivo by an antisense oligonucleotide also increased α-exon inclusion. These results suggest that PTB plays a direct role in α-exon splicing.