title: Alternative splicing of a previously unidentified CFTR exon introduces an in-frame stop codon 5' of the R region.
abstract: The cystic fibrosis transmembrane conductance regulator (CFTR) has been extensively characterized as the carrier of the basic defect in cystic fibrosis. CFTR is part of a growing family of proteins encoded by a single gene, the variant isoforms of which are generated by alternative splicing or RNA editing. We have analyzed the CFTR mRNA in the region of exons 10-11 in T84 cells and detected an alternatively spliced exon (10b) accounting for about 5% of the CFTR mRNA. The exon 10b found in both the human and mice genomes, introduces an in-frame stop codon. The resulting mRNA is translated into a truncated CFTR protein, identified in T84 cells by immunoprecipitation with the CFTR-specific monoclonal antibody MATG 1061. The insertion of a differentially spliced exon carrying an in-frame stop codon is a novel cellular mechanism for the production of a protein sharing common sequences with another, but having different properties and functions.
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
authors.forename: C A
authors.initials: CA
authors.lastname: Melo
authors.forename: C
authors.initials: C
authors.lastname: Serra
authors.forename: V
authors.initials: V
authors.lastname: Stoyanova
authors.forename: C
authors.initials: C
authors.lastname: Aguzzoli
authors.forename: D
authors.initials: D
authors.lastname: Faraguna
authors.forename: A
authors.initials: A
authors.lastname: Tamanini
authors.forename: G
authors.initials: G
authors.lastname: Berton
authors.forename: G
authors.initials: G
authors.lastname: Cabrini
authors.forename: F E
authors.initials: FE
authors.lastname: Baralle
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D003001:Cloning, Molecular; D003062:Codon; D003110:Colonic Neoplasms; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005091:Exons; D006801:Humans; D007163:Immunosorbent Techniques; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012326:RNA Splicing; D012333:RNA, Messenger / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; C505032:CFTR protein, human; D003062:Codon; D008565:Membrane Proteins; D012333:RNA, Messenger; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004247:DNA