BETA-SPECTRIN IN HUMAN SKELETAL-MUSCLE - TISSUE-SPECIFIC DIFFERENTIAL PROCESSING OF 3' BETA-SPECTRIN PRE-MESSENGER-RNA GENERATES A BETA-SPECTRIN ISOFORM WITH A UNIQUE CARBOXYL TERMINUS

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  • 25 November 1990
    • journal article
    • research article
    • Vol. 265  (33) , 20449-20454
Abstract
Spectrin, an important component of the mammalian erythrocyte membrane skeleton, is a heterodimeric protein with .alpha. and .beta. subunits of 280 and 246 kDa, respectively. Spectrin-like proteins have also been demonstrated in a wide variety of nonerythroid cells. To examine the hypothesis that nonerythroid .beta. spectrins may be encoded by the "erythroid" .beta. spectrin gene, we have isolated cDNA clones from a human fetal skeletal muscle library by hybridization to a previously described red cell .beta. spectrin cDNA. Detailed comparison of muscle and erythroid .beta. spectrin cDNAs has revealed sequence identity over the majority of their lengths, confirming that they are the product of the same gene. However, there is a sharp divergence in sequence at their 3''ends. A consequence of this divergence is the replacement of the carboxyl terminus of erythroid .beta. spectrin with a different, longer carboxyl-terminal domain in skeletal muscle. We hypothesize that tissue-specific differential polyadenylation leads to the selective activation of a donor splice site within the .beta. spectrin coding sequence, splicing downstream nonerythroid exons into the mature muscle .beta. spectrin mRNA. We predict that replacement, nonerythroid cells, of the .beta. spectrin carboxyl terminus, known to participate in spectrin self-association and phosphorylation, has significant functional consequences. These data may explain previously reported nonerythroid .beta. spectrin isoforms that resemble red cell .beta. spectrin by immunochemical analysis.