Alternative splicing of intron 23 of the human cystic fibrosis transmembrane conductance regulator gene resulting in a novel exon and transcript coding for a shortened intracytoplasmic C terminus.

Publication Type	Academic Article
Authors	Yoshimura K, Chu C, Crystal R
Journal	J Biol Chem
Volume	268
Issue	1
Pagination	686-90
Date Published	01/05/1993
ISSN	0021-9258
Keywords	Alternative Splicing, Cystic Fibrosis, Introns, Membrane Proteins, Transcription, Genetic
Abstract	The cystic fibrosis transmembrane conductance regulator (CFTR) gene, the gene responsible for the lethal hereditary disorder cystic fibrosis, codes for a membrane protein functioning as a cAMP-regulated Cl- channel. Evaluation of human CFTR mRNA transcripts from epithelial and nonepithelial cells demonstrated a CFTR cDNA containing a 260-base pair (bp) insertion between the known CFTR exons 23 and 24, introducing a premature stop codon that would result in a CFTR protein shortened by 61 amino acids at the carboxyl terminus compared to that expected from the normal reported human CFTR coding sequences. Sequence analysis of intron 23 of the CFTR gene demonstrated that the 260-bp insertion (named exon 24a), a part of the reported intron 23 and located consecutive to exon 24, is likely generated by an alternative splice acceptor site. The exon 24a+ CFTR mRNA transcripts represented 3-16% of the total CFTR transcripts in epithelial and nonepithelial cells. These observations suggest an unexpected plasticity of expression of the CFTR gene, where alternative splicing of precursor CFTR mRNA transcripts permits the use of an alternative exon derived from a genomic segment previously believed to function as an intron.
PubMed ID	7678008