title: Cryptic splice site usage in exon 7 of the human fibrinogen Bbeta-chain gene is regulated by a naturally silent SF2/ASF binding site within this exon.
abstract: In this work we report the identification of a strong SF2/ASF binding site within exon 7 of the human fibrinogen Bbeta-chain gene (FGB). Its disruption in the wild-type context has no effect on exon recognition. However, when the mutation IVS7 + 1G>T--initially described in a patient suffering from congenital afibrinogenemia--is present, this SF2/ASF binding site is critical for cryptic 5'ss (splice site) definition. These findings, besides confirming and extending previous results regarding the effect of SF2/ASF on cryptic splice site activation, identify for the first time an enhancer sequence in the FGB gene specific for cryptic splice site usage. Taken together, they suggest the existence of a splicing-regulatory network that is normally silent in the FGB natural splicing environment but which can nonetheless influence splicing decisions when local contexts allow. On a more general note, our conclusions have implications for the evolution of alternative splicing processes and for the development of methods to control aberrant splicing in the context of disease-causing mutations.
authors.affiliation: Department of Biology, University of Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Spena
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Tenchini
authors.forename: Emanuele
authors.initials: E
authors.lastname: Buratti
mesh_terms: D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D005091:Exons; D005340:Fibrinogen / Q000235:genetics* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D017354:Point Mutation; D022821:RNA Splice Sites / Q000235:genetics; D012326:RNA Splicing; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D000068103:Serine-Arginine Splicing Factors; D014162:Transfection
chemical_list: C115499:BBeta fibrinogen; D009687:Nuclear Proteins; D022821:RNA Splice Sites; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D000068103:Serine-Arginine Splicing Factors; D005340:Fibrinogen