Polypyrimidine tract-binding protein down-regulates fibroblast growth factor receptor 1 alpha-exon inclusion.
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.
Jin
Wei
W
Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Bruno
Ivone G
IG
Xie
Tong-Xin
TX
Sanger
Laura J
LJ
Cote
Gilbert J
GJ
D017398:Alternative Splicing / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D000818:Animals; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005091:Exons / Q000187:drug effects / Q000235:genetics; D006801:Humans; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D038941:Polypyrimidine Tract-Binding Protein / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D012322:RNA Precursors / Q000187:drug effects / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016376:Oligonucleotides, Antisense; D020033:Protein Isoforms; D012322:RNA Precursors; D017468:Receptors, Fibroblast Growth Factor; D038941:Polypyrimidine Tract-Binding Protein; C496348:FGFR1 protein, human; C496349:Fgfr1 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1