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Polypyrimidine Tract-Binding Protein Down-Regulates Fibroblast Growth Factor Receptor 1 -Exon Inclusion¹

Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas M. D. Anderson Cancer Center [W. J., I. G. B., T-X. X., L. J. S., G. J. C.], and The University of Texas Graduate School of Biomedical Sciences, Houston, Texas 77030 [I. G. B., G. J. C.]

Exclusion of the -exon by alternative RNA splicing of the fibroblast growth factor receptor 1 (FGFR1) primary transcript leads to the production of FGFR1ß. Glial cell transformation is associated with a progressive increase in FGFR1ß 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 -exon skipping, and a reduction in PTB increased -exon inclusion. Targeted disruption of PTB interaction with FGFR1 precursor RNA in vivo by an antisense oligonucleotide also increased -exon inclusion. These results suggest that PTB plays a direct role in -exon splicing.

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