Alternative splicing of a previously unidentified CFTR exon introduces an in-frame stop codon 5' of the R region

AbstractThe 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 lOb found in both the human and mice genomes, introduces an inframe 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 inframe stop codon is a novel cellular mechanism for the production of a protein sharing common sequences with another, but having different properties and functions