Splicing of two alternative exon pairs in beta-tropomyosin pre-mRNA is independently controlled during myogenesis.
Two known tissue-specific tropomyosin (TM) isoforms are produced from the rodent beta-TM gene. Skeletal muscle beta-TM uses the alternative exons 6b and 9a and the exon 9a-associated poly(A) site. Fibroblast and smooth muscle TM-1 use exons 6a and 9b and the exon-9b associated poly(A) site. We have identified a new skeletal muscle beta-TM isoform, beta-TM2. beta-TM2 contains exon 6b (muscle) and exon 9b (nonmuscle). Full-length beta-TM2 cDNA clones were isolated from a cDNA library of mouse muscle BC3H1 cells. Its mRNA was also found in mouse skeletal muscle tissue but not in other tissues. beta-TM2 mRNA level and protein synthesis are differentiation-dependent, with a transient high level in the early stages of myogenesis both in BC3H1 cells and in mouse embryo limbs. Trace amounts of beta-TM3 mRNA, the other hybrid form (exons 6a + 9a), were found in less differentiated BC3H1 cells, mouse uterus, heart, and 3T3 fibroblasts but not skeletal muscle tissue. Thus, the selection of the two alternative exons appears to be controlled independently. Furthermore, during myogenesis, there is a sequential switch in the internal alternative exon, the terminal exon, and the poly(A) site from the nonmuscle to the muscle type.
Wang
Y C
YC
Department of Biochemistry, University of Iowa College of Medicine, Iowa City 52242.
Rubenstein
P A
PA
D000595:Amino Acid Sequence; D000818:Animals; D001345:Autoradiography; D001483:Base Sequence; D015152:Blotting, Northern; D002454:Cell Differentiation; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D005091:Exons; D051379:Mice; D008969:Molecular Sequence Data; D009132:Muscles / Q000166:cytology / Q000378:metabolism*; D012322:RNA Precursors / Q000378:metabolism*; D015347:RNA Probes; D012323:RNA Processing, Post-Transcriptional; D012326:RNA Splicing; D016372:RNA, Antisense / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D014335:Tropomyosin / Q000235:genetics*
D012322:RNA Precursors; D015347:RNA Probes; D016372:RNA, Antisense; D012333:RNA, Messenger; D014335:Tropomyosin; D004247:DNA