Beta spectrin in human skeletal muscle. Tissue-specific differential processing of 3' beta spectrin pre-mRNA generates a beta spectrin isoform with a unique carboxyl terminus.
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, in 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.
Winkelmann
J C
JC
Department of Medicine, University of Minnesota, Minneapolis 55455.
Costa
F F
FF
Linzie
B L
BL
Forget
B G
BG
D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D004912:Erythrocytes / Q000378:metabolism; D005091:Exons; D005333:Fetus; D015723:Gene Library; D005796:Genes; D006801:Humans; D008099:Liver / Q000378:metabolism; D008969:Molecular Sequence Data; D009132:Muscles / Q000378:metabolism*; D015345:Oligonucleotide Probes; D012322:RNA Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D013049:Spectrin / Q000235:genetics*
D015345:Oligonucleotide Probes; D012322:RNA Precursors; D012333:RNA, Messenger; D013049:Spectrin