Abstract
Exclusion of the alpha-exon by alternative RNA splicing of the fibroblast growth factor receptor 1 (FGFR1) primary transcript leads to the production of FGFR1beta. Glial cell transformation is associated with a progressive increase in FGFR1beta 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 alpha-exon skipping, and a reduction in PTB increased alpha-exon inclusion. Targeted disruption of PTB interaction with FGFR1 precursor RNA in vivo by an antisense oligonucleotide also increased alpha-exon inclusion. These results suggest that PTB plays a direct role in alpha-exon splicing.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Alternative Splicing / drug effects
-
Alternative Splicing / genetics
-
Alternative Splicing / physiology*
-
Animals
-
Cell Line, Tumor
-
Down-Regulation
-
Exons / drug effects
-
Exons / genetics
-
Humans
-
Mice
-
Oligonucleotides, Antisense / genetics
-
Oligonucleotides, Antisense / pharmacology
-
Polypyrimidine Tract-Binding Protein / biosynthesis
-
Polypyrimidine Tract-Binding Protein / genetics
-
Polypyrimidine Tract-Binding Protein / physiology*
-
Protein Isoforms / biosynthesis
-
Protein Isoforms / genetics
-
RNA Precursors / drug effects
-
RNA Precursors / genetics
-
Receptor Protein-Tyrosine Kinases / biosynthesis
-
Receptor Protein-Tyrosine Kinases / genetics*
-
Receptor, Fibroblast Growth Factor, Type 1
-
Receptors, Fibroblast Growth Factor / biosynthesis
-
Receptors, Fibroblast Growth Factor / genetics*
-
Reverse Transcriptase Polymerase Chain Reaction
Substances
-
Oligonucleotides, Antisense
-
Protein Isoforms
-
RNA Precursors
-
Receptors, Fibroblast Growth Factor
-
Polypyrimidine Tract-Binding Protein
-
FGFR1 protein, human
-
Fgfr1 protein, mouse
-
Receptor Protein-Tyrosine Kinases
-
Receptor, Fibroblast Growth Factor, Type 1