Control of BEK and K-SAM splice sites in alternative splicing of the fibroblast growth factor receptor 2 pre-mRNA.
The fibroblast growth factor receptor 2 gene pre-mRNA can be spliced by using either the K-SAM exon or the BEK exon. The exon chosen has a profound influence on the ligand-binding specificity of the receptor obtained. Cells make a choice between the two alternative exons by controlling use of both exons. Using fibroblast growth factor receptor 2 minigenes, we have shown that in cells normally using the K-SAM exon, the BEK exon is not used efficiently even in the absence of the K-SAM exon. This is because these cells apparently express a titratable repressor of BEK exon use. In cells normally using the BEK exon, the K-SAM exon is not used efficiently even in the absence of a functional BEK exon. Three purines in the K-SAM polypyrimidine tract are at least in part responsible for this, as their mutation to pyrimidines leads to efficient use of the K-SAM exon, while mutating the BEK polypyrimidine tract to include these purines stops BEK exon use.
Gilbert
E
E
INSERM U211, Institut de Biologie, Centre Hospitalier Régional de Nantes, France.
Del Gatto
F
F
Champion-Arnaud
P
P
Gesnel
M C
MC
Breathnach
R
R
D017398:Alternative Splicing; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005091:Exons; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D015603:Keratinocytes / Q000378:metabolism; D008969:Molecular Sequence Data; D009694:Nucleic Acid Precursors / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*; D013329:Structure-Activity Relationship
D009694:Nucleic Acid Precursors; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; C496353:FGFR2 protein, human; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2