Alternative splicing of brain-specific PTB defines a tissue-specific isoform pattern that predicts distinct functional roles.
Splicing of neural-specific exons is differentially regulated in neuronal and non-neuronal cells. The polypyrimidine tract binding protein (PTB) has been implicated as a negative regulator for exon splicing, whereas the brain-specific homolog of PTB, termed nPTB, promotes exon splicing exclusively in neurons. We have now isolated a novel mRNA splice variant of nPTB from non-neuronal cells. In contrast to the neural nPTB transcript, the expression of this novel isoform was absent from brain tissue and was generated in non-neuronal cells by alternative splicing to include five additional amino acid residues encoded by exon 9. In addition, we identified a brain-specific transcript containing a novel, alternatively spliced, internal exon 10. The exclusion of this 34-nucleotide exon 10 in non-neuronal tissues generates a premature termination codon and results in the truncation of the open reading frame. Our findings suggest that alternative splicing of nPTB has an important role in regulation of tissue-specific gene expression and thus in the functional activity of nPTB in neuronal and non-neuronal cells.
Rahman
Lambratu
L
Center for Cancer Research, National Cancer Institute, National Institute of Health, Bethesda, Maryland 20892, USA.
Bliskovski
Valery
V
Reinhold
William
W
Zajac-Kaye
Maria
M
D017398:Alternative Splicing; D000818:Animals; D001921:Brain / Q000378:metabolism*; D005333:Fetus / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity / Q000235:genetics; D038941:Polypyrimidine Tract-Binding Protein / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism
D020033:Protein Isoforms; D038941:Polypyrimidine Tract-Binding Protein