ESRP1 and 2 bind FGFR2 pre-mRNA to promote FGFR2b maturation and expression

Stable Identifier
R-HSA-6803527
Type
Reaction [binding]
Species
Homo sapiens
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Expression of FGFR2 IIIb splice variant is characteristic of epithelial cells. A number of cis-acting elements have been identified in the FGFR2 pre-mRNA that are required for correct expression of the IIIb isoform and repression of the mesenchymal IIIc form (Muh et al, 2002; Hovhannisyan and Carstens, 2005; Hovhannisyan et al, 2006). These include the ISAR and ISE/ISS elements 1-3 in the region between exon 8 and exon 9 of the pre-mRNA. ESRP1 and ESRP2 are RNA-binding mRNA splicing factors that promote epithelial-specific IIIb splicing by binding to the ISE/ISS-3 sequence (Warzecha et al, 2009). A complex of RBFOX2, hnRNPH1 and hnRNPF may cooperate with the ESRP proteins to stimulate IIIb-specific splicing by binding to adjacent exonic GGG motifs (Baraniak et al, 2006; Mauger et al, 2008). This RBFOX2-hnRNP complex appears to compete with the IIIc-promoting trans-acting factor ASF/SF2 for binding to these exonic sites (Mauger et al, 2008). Other factors that appear to contribute to IIIb-specific splicing include hnRNPM, TIA1 and TIAL1, although their precise roles remain to be elucidated (Hovhannisyan and Carstens, 2007; Del Gatto-Konczak et al, 2000; Newman et al, 2006).

Literature References
PubMed ID Title Journal Year
16449636 Fox-2 mediates epithelial cell-specific fibroblast growth factor receptor 2 exon choice

Baraniak, AP, Chen, JR, Garcia-Blanco, MA

Mol. Cell. Biol. 2006
18573884 hnRNP H and hnRNP F complex with Fox2 to silence fibroblast growth factor receptor 2 exon IIIc

Mauger, DM, Lin, C, Garcia-Blanco, MA

Mol. Cell. Biol. 2008
17959601 Heterogeneous ribonucleoprotein m is a splicing regulatory protein that can enhance or silence splicing of alternatively spliced exons

Hovhannisyan, RH, Carstens, RP

J. Biol. Chem. 2007
16410617 Characterization of sequences and mechanisms through which ISE/ISS-3 regulates FGFR2 splicing

Hovhannisyan, RH, Warzecha, CC, Carstens, RP

Nucleic Acids Res. 2006
12393912 A Non-sequence-specific double-stranded RNA structural element regulates splicing of two mutually exclusive exons of fibroblast growth factor receptor 2 (FGFR2)

Muh, SJ, Hovhannisyan, RH, Carstens, RP

J. Biol. Chem. 2002
16603716 Identification of RNA-binding proteins that regulate FGFR2 splicing through the use of sensitive and specific dual color fluorescence minigene assays

Newman, EA, Muh, SJ, Hovhannisyan, RH, Warzecha, CC, Jones, RB, McKeehan, WL, Carstens, RP

RNA 2006
10938105 The RNA-binding protein TIA-1 is a novel mammalian splicing regulator acting through intron sequences adjacent to a 5' splice site

Del Gatto-Konczak, F, Bourgeois, CF, Le Guiner, C, Kister, L, Gesnel, MC, Stévenin, J, Breathnach, R

Mol. Cell. Biol. 2000
19285943 ESRP1 and ESRP2 are epithelial cell-type-specific regulators of FGFR2 splicing

Warzecha, CC, Sato, TK, Nabet, B, Hogenesch, JB, Carstens, RP

Mol. Cell 2009
15601847 A novel intronic cis element, ISE/ISS-3, regulates rat fibroblast growth factor receptor 2 splicing through activation of an upstream exon and repression of a downstream exon containing a noncanonical branch point sequence

Hovhannisyan, RH, Carstens, RP

Mol. Cell. Biol. 2005
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