Tropomyosin 3 increases striated muscle isoform diversity.
Tropomyosin (TM), a component of the thin filament of the sarcomere, is encoded by a four-member multigene family: alpha-TM, beta-TM, TPM 3, and TPM 4. The alpha-TM, beta-TM, and TPM 3 genes each utilize an alternative splicing mechanism to encode a striated muscle isoform. Although the alpha-TM and beta-TM striated muscle isoforms are well characterized, relatively little is known about the TPM 3 isoform. We cloned and sequenced the murine TPM 3 cDNA and found that it exhibits a 93% nucleotide homology and 99% amino acid homology to the human sequence. Results show that, unlike humans, TPM 3 is not expressed in any developmental stage of murine hearts. TPM 3 message is expressed in slow-twitch skeletal muscle but is not found in representative fast-twitch musculature. The soleus, a representative slow-twitch muscle, expresses transcript levels of 65% beta-TM, 15% alpha-TM, and 20% TPM 3, but the TPM 3 protein accounts for approximately 31% of the total striated tropomyosin in slow-twitch muscle. In fast-twitch muscle, alpha-TM comprises 71% of the total striated muscle TM protein, and beta-TM comprises 29%. The results demonstrate that a translational mechanism regulates the production of the TM proteins, with beta-TM message not being efficiently translated. The unique distribution pattern of TPM 3 adds to the diversity of the tropomyosin family and strongly suggests functional significance for the different striated muscle TM isoforms.
Pieples
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Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0524, USA.
Wieczorek
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DF
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000032:analysis / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics; D017422:Sequence Analysis, DNA; D014335:Tropomyosin / Q000235:genetics*
D018076:DNA, Complementary; D020033:Protein Isoforms; C498783:TPM3 protein, human; C411923:Tpm3 protein, mouse; D014335:Tropomyosin