Identification of an intronic splicing enhancer essential for the inclusion of FGFR2 exon IIIc

Puneet Seth, Heather B. Miller, Erika L. Lasda, James L. Pearson, Mariano Garcia-Blanco

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The ligand specificity of fibroblast growth factor receptor 2 (FGFR2) is determined by the alternative splicing of exons 8 (IIIb) or 9 (IIIc). Exon IIIb is included in epithelial cells, whereas exon IIIc is included in mesenchymal cells. Although a number of cis elements and trans factors have been identified that play a role in exon IIIb inclusion in epithelium, little is known about the activation of exon IIIc in mesenchyme. We report here the identification of a splicing enhancer required for IIIc inclusion. This 24-nucleotide (nt) downstream intronic splicing enhancer (DISE) is located within intron 9 immediately downstream of exon IIIc. DISE was able to activate the inclusion of heterologous exons rat FGFR2 IIIb and human β-globin exon 2 in cell lines from different tissues and species and also in HeLa cell nuclear extracts in vitro. DISE was capable of replacing the intronic activator sequence 1 (IAS1), a known IIIb splicing enhancer and vice versa. This fact, together with the requirement for DISE to be close to the 5′-splice site and the ability of DISE to promote binding of U1 snRNP, suggested that IAS1 and DISE belong to the same class of cis-acting elements.

Original languageEnglish (US)
Pages (from-to)10058-10067
Number of pages10
JournalJournal of Biological Chemistry
Volume283
Issue number15
DOIs
StatePublished - Apr 11 2008
Externally publishedYes

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Receptor, Fibroblast Growth Factor, Type 2
Exons
U1 Small Nuclear Ribonucleoproteins
RNA Splice Sites
Globins
Alternative Splicing
Mesoderm
Cell Extracts
HeLa Cells
Introns
Epithelium
Nucleotides
Epithelial Cells
Chemical activation
Cells
Tissue
Ligands
Cell Line

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Identification of an intronic splicing enhancer essential for the inclusion of FGFR2 exon IIIc. / Seth, Puneet; Miller, Heather B.; Lasda, Erika L.; Pearson, James L.; Garcia-Blanco, Mariano.

In: Journal of Biological Chemistry, Vol. 283, No. 15, 11.04.2008, p. 10058-10067.

Research output: Contribution to journalArticle

Seth, Puneet ; Miller, Heather B. ; Lasda, Erika L. ; Pearson, James L. ; Garcia-Blanco, Mariano. / Identification of an intronic splicing enhancer essential for the inclusion of FGFR2 exon IIIc. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 15. pp. 10058-10067.
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