title: Conserved use of a non-canonical 5' splice site (/GA) in alternative splicing by fibroblast growth factor receptors 1, 2 and 3.
abstract: The two classes of sequences for recognition and splicing of pre-mRNA in eukaryotes, GT-AG and AT-AC, are characterized by the nearly invariant dinucleotides present at the extreme 5' (donor) and 3' (acceptor) ends of the intron. Amongst GT-AG introns, which comprise the vast majority, the more extended consensus sequence at the 5' splice site isACAG/GTAGAGT (where / indicates the exon-intron boundary). This sequence is complementary to part of the U1 snRNA and is important in intron recognition. We have determined the genomic structure of the mouse fibroblast growth factor receptor 2 gene (Fgfr2) and identified a divergent 5' splice site (ACA/GAAAGT), conserved in FGFR1 , - 2 and - 3 from humans, mice and Xenopus that is used for alternative splicing of a hexanucleotide sequence, encoding Val-Thr, at the end of exon 10. This is the only example known of the use of /GA in vertebrate splicing. Similarities to a splice site in the Antennapedia gene of Drosophila suggest that this variant motif is involved in alternative splicing of short sequences at the 5' splice site. Inclusion or exclusion of the Val-Thr dipeptide may play an important role in controlling FGFR signalling through the Ras/MAPK pathway.
authors.affiliation: Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK.
authors.forename: S R
authors.initials: SR
authors.lastname: Twigg
authors.forename: H D
authors.initials: HD
authors.lastname: Burns
authors.forename: M
authors.initials: M
authors.lastname: Oldridge
authors.forename: J K
authors.initials: JK
authors.lastname: Heath
authors.forename: A O
authors.initials: AO
authors.lastname: Wilkie
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000502:physiology; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics* / Q000502:physiology
chemical_list: D017468:Receptors, Fibroblast Growth Factor; C496348:FGFR1 protein, human; C496353:FGFR2 protein, human; C496365:FGFR3 protein, human; C496349:Fgfr1 protein, mouse; C496354:Fgfr2 protein, mouse; C496366:Fgfr3 protein, mouse; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; D051498:Receptor, Fibroblast Growth Factor, Type 3