Glioblastoma cell-specific expression of fibroblast growth factor receptor-1beta requires an intronic repressor of RNA splicing.

Abstract

The fibroblast growth factor receptor-1 (FGFR-1) primary transcript is alternatively processed to produce receptors that vary in their ligand affinity and specificity. A high affinity form of this receptor--FGFR-1beta--that lacks the alpha exon is observed on the neoplastic transformation of glial cells. In this study, we have identified a 62-bp sequence located 97 bp downstream from the alpha exon that is required for the exclusion of this exon in a human glioblastoma cell line. Deletion or mutation of this sequence is sufficient to allow enhanced inclusion of the alpha exon or a heterologous exon in glioblastoma cells. Therefore, it would appear that this sequence element plays a key role in the glioblastoma-specific splicing to form FGFR-1beta mRNA.