Identification of an intronic splicing enhancer essential for the inclusion of FGFR2 exon IIIc.
Enviado por Mariano Garcia-Blanco el
Título | Identification of an intronic splicing enhancer essential for the inclusion of FGFR2 exon IIIc. |
Publication Type | Journal Article |
Year of Publication | 2008 |
Autores | Seth, P, Miller, HB, Lasda, EL, Pearson, JL, García-Blanco, MA |
Journal | J Biol Chem |
Volume | 283 |
Issue | 15 |
Pagination | 10058-67 |
Date Published | 2008 Apr 11 |
ISSN | 0021-9258 |
Palabras clave | Alternative Splicing, Animals, Enhancer Elements, Genetic, Epithelium, Exons, Globins, HeLa Cells, Humans, Mesoderm, Mice, Organ Specificity, Rats, Receptor, Fibroblast Growth Factor, Type 2, Ribonucleoprotein, U1 Small Nuclear |
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 beta-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. |
DOI | 10.1074/jbc.M800087200 |
Alternate Journal | J. Biol. Chem. |
PubMed ID | 18256031 |