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Identification of an intronic splicing enhancer essential for the inclusion of FGFR2 exon IIIc.
J Biol Chem. 2008 Apr 11; 283(15):10058-67.JB

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.

Authors+Show Affiliations

Department of Molecular Genetics and Microbiology, and Center for RNA Biology, Duke University Medical Center, Durham, NC 27710, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

18256031

Citation

Seth, Puneet, et al. "Identification of an Intronic Splicing Enhancer Essential for the Inclusion of FGFR2 Exon IIIc." The Journal of Biological Chemistry, vol. 283, no. 15, 2008, pp. 10058-67.
Seth P, Miller HB, Lasda EL, et al. Identification of an intronic splicing enhancer essential for the inclusion of FGFR2 exon IIIc. J Biol Chem. 2008;283(15):10058-67.
Seth, P., Miller, H. B., Lasda, E. L., Pearson, J. L., & Garcia-Blanco, M. A. (2008). Identification of an intronic splicing enhancer essential for the inclusion of FGFR2 exon IIIc. The Journal of Biological Chemistry, 283(15), 10058-67. https://doi.org/10.1074/jbc.M800087200
Seth P, et al. Identification of an Intronic Splicing Enhancer Essential for the Inclusion of FGFR2 Exon IIIc. J Biol Chem. 2008 Apr 11;283(15):10058-67. PubMed PMID: 18256031.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification of an intronic splicing enhancer essential for the inclusion of FGFR2 exon IIIc. AU - Seth,Puneet, AU - Miller,Heather B, AU - Lasda,Erika L, AU - Pearson,James L, AU - Garcia-Blanco,Mariano A, Y1 - 2008/02/06/ PY - 2008/2/8/pubmed PY - 2008/5/29/medline PY - 2008/2/8/entrez SP - 10058 EP - 67 JF - The Journal of biological chemistry JO - J Biol Chem VL - 283 IS - 15 N2 - 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. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/18256031/Identification_of_an_intronic_splicing_enhancer_essential_for_the_inclusion_of_FGFR2_exon_IIIc_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(20)57078-6 DB - PRIME DP - Unbound Medicine ER -