Alternative splicing of human dystrophin mRNA generates isoforms at the carboxy terminus

Abstract

DYSTROPHIN is the protein product of the Duchenne/Becker muscular dystrophy locus. It has a relative molecular mass of 427,000 and is encoded by a large RNA transcript processed from more than 65 exons spread over two million base pairs of the human X chromosome^1–5. We have used the polymerase chain reaction⁶ to see whether any of these exons are used alternatively in the different tissues that express dystrophin. As reported for rat dystrophin⁷, we find that the first exon of the human dystrophin transcript is different in brain and muscle, indicating that dystrophin expression could be differentially regulated in these tissues by usage of distinct promoters. The 3′ end of the dystrophin transcript can be alternatively spliced to create numerous isoforms differing at their carboxy 1 domains; this is the only domain of dystrophin that does not share any similarity with the related cytoskeletal α-actinins³. These alternative transcripts yield dystrophin molecules which may interact with different proteins of the tissues expressing dystrophin.