Disease relevance of TPM3

• We have previously reported a Met9Arg mutation in the human skeletal muscle alpha tropomyosin gene (TPM3) associated with autosomal dominant nemaline myopathy [Nat. Genet. 9 (1995) 75] [1].
• The Escherichia coli produced chicken gizzard beta-tropomyosin mutant, CSM-beta (1/8/12-227), bound caldesmon about 2-fold stronger than a similar mutant of residues 8-200 [2].

High impact information on TPM3

• The beta-tropomyosin gene in chicken contains two mutually exclusive exons (exons 6A and 6B) which are used by the splicing apparatus in myogenic cells, respectively, before (myoblast stage) and after (myotube stage) differentiation [3].
• Exons 6A and 6B of the chicken beta-tropomyosin gene are mutually exclusive and selected in a tissue-specific manner [4].
• The chicken beta-tropomyosin gene contains 11 exons, two of which are spliced into mRNA only in skeletal muscle [5].
• Under this condition, the binding of tropomyosin 3 (3a + 3b) to actin filaments was significantly weaker than that of tropomyosin 1 or 2 [6].
• Thus, the skeletal muscle tropomyosin 3' UTR induces transdifferentiation into a striated muscle phenotype in a cell-type-specific context [7].

Biological context of TPM3

• A clone isolated from a skeletal muscle cDNA library contains the complete protein-coding sequence of the 284-amino-acid skeletal muscle beta-tropomyosin together with 72 bases of 5' untranslated sequence and nearly the entire 3' untranslated region (about 660 bases), lacking only the last 4 bases and the poly(A) tail [8].
• Amino acid sequence of chicken gizzard beta-tropomyosin. Comparison of the chicken gizzard, rabbit skeletal, and equine platelet tropomyosins [9].
• Skeletal muscle beta-tropomyosin, smooth muscle alpha-tropomyosin, and a low molecular weight fibroblast tropomyosin are generated by alternatively splicing RNA transcripts of the chicken tropomyosin 1 (TM 1) gene (Forry-Schaudies, S., Maihle, N. J., and Hughes, S. H. (1990) J. Mol. Biol. 211; 321-330) [10].
• Normally the pectoralis major muscle represses synthesis of both beta-tropomyosin and leg-type troponin T during late embryonic development [11].
• Specific changes in the RNA population during myogenesis were further investigated by quantitation of the synthetic capacity (messenger RNA levels) per cell for alpha- and beta-tropomyosin [12].

Anatomical context of TPM3

• Isolation and characterization of related cDNA clones encoding skeletal muscle beta-tropomyosin and a low-molecular-weight nonmuscle tropomyosin isoform [8].
• Chicken gizzard beta-tropomyosin has the same chain length (284 residues) as other muscle tropomyosins, and is most closely related to the beta component of rabbit skeletal muscle [9].
• Cell-free translation and immunoprecipitation demonstrated an approximately 40-fold increase in messenger RNA levels per nucleus for alpha- and beta-tropomyosin after fusion in the terminally differentiated myotubes [12].
• Recently, Sirand-Pugnet et al. reported the importance of an additional intronic sequence, an (A/U)GGG repeat in chicken beta-tropomyosin that is a binding site for a protein required for spliceosome assembly [13].
• By analyzing the splicing pattern of hybrid chicken/rat beta-TM constructions transfected into both quail and mouse cell lines, we demonstrate that chicken beta-tropomyosin exon 6A is flanked by stronger splicing signals than rat exon 6A, thus leading to the misregulation of splicing in heterologous cells [14].

Associations of TPM3 with chemical compounds

• In vitro splicing of mutually exclusive exons from the chicken beta-tropomyosin gene: role of the branch point location and very long pyrimidine stretch [5].

Enzymatic interactions of TPM3

• The alpha-tropomyosin subunit from rabbit and chicken skeletal muscle was phosphorylated about five times faster than the beta-tropomyosin subunit [15].

Other interactions of TPM3

• When the tropomyosin 3' UTR is expressed in osteoblasts, less skeletal muscle tropomyosin is expressed, and titin expression is delayed [7].
• In all other areas of the muscle examined only fast myosin light chains, beta-tropomyosin and the alpha-fast form of tropomyosin, are found [16].
• Fibers derived from either population synthesized the embryonic myosin heavy chain in addition to alpha-fast and beta-tropomyosin [17].
• UV irradiation of mixtures of calcyclin and gizzard beta beta-tropomyosin labeled with benzophenone-iodoacetamide at Cys36, with or without actin, produced crosslinks between tropomyosin chains and calcyclin monomers only in the presence of Ca2+ [18].

Analytical, diagnostic and therapeutic context of TPM3

• After denervation, however, the muscle relaxes its ongoing repression of these proteins and significant amounts of both beta-tropomyosin and leg-type troponin T are synthesized by the muscle [11].

References