Tropomyosin genes

Planitzer SA, Machl AW, Schindler D, Kubbies M. 1998. Small deletions in the regulatory 3 UTR of the human alpha-tropomyosin gene identified by differential display. Mol Cell Probes 12(1) 35. 

H. Tuunanen, J. Kuusisto, J. Toikka, P. Jaaskelainen, P. Maijamaki, K. Peuhkurinen, T. Viljanen, P. Sipola, K.Q. Stolen, J. Hannukainen, P. Nuutila, M. Laakso, J. Knuuti, Myocardial perfusion, oxidative metabolism, and free fatty acid uptake in patients with hypertrophic cardiomyopathy attributable to the Asp175Asn mutation in the alpha-tropomyosin gene A positron emission tomography study, J. Nucl. Cardiol. 14(2007) 354-365. 

Wieczorek, D.E, Smith, C.W. and Nadal-Ginard, B. The rat alpha-tropomyosin gene generates a minimum of six different mRNAs coding for striated, smooth, and nonmuscle isoforms by alternative splicing (1988) Mol. Cell Biol. 8, 679-94... 

Ruiz-Opazo, N., and Nadal-Ginard, B. (1987). Alpha-tropomyosin gene organization. Alternative splicing of duplicated iso type-specific exons accounts for the production of smooth and striated muscle isoforms./. Biol. Chem. 262, 4755—4765. 

Lin, M., Nguyen, H., Dybala, C., and Storti, R. (1996). Myocyte-specific enhancer factor 2 acts cooperatively with a muscle activator region to regulate Drosophila tropomyosin gene muscle expression. Proc. Natl. Acad. Sci. USA 97 4623-4628. 

Fleenor, D.E, Hickman, KH., Lindquester, G.]. Devlin, R.B. (1992). Avian cardiac tropomyosin gene produces tissue-specific isoforms through alternative RNA splicing.. Musde Res. Cell Motility, 13, 55-63. 

Libri, D., Mouly, V., Lemonnier, M. Fiszman, M.Y. (1990). A nonmuscle tropomyosin is encoded by the smooth/skeletal -tropomyosin gene and its RNA is transcribed from an internal promoter. ]. Biol Chem., 265, 3471-3. 

Libri, D., Piseri, A. 8e Fiszman, M.Y. (1991). Tissue-specific splicing in vivo of the -tropomyosin gene-dependence on an RNA secondary structure. Scietux, 252, 1842-5. 

Figure 49-13. Simplified scheme of the causation of familial hypertrophic cardiomyopathy (MIM 192600) due to mutations in the gene encoding fi-myosin heavy chain. Mutations in genes encoding other proteins, such as the troponins, tropomyosin, and cardiac myosin-binding protein C can also cause this condition. Mutations in genes encoding yet other proteins (eg, dystrophin) are involved in the causation of dilated cardiomyopathy.

Fig. 1.48. Differential splicing in muscle proteins, a) The troponin gene of rats possess 18 exons that encode 258 amino acids. Different subtypes of troponin are found in various types of muscle tissue.The exons 1-3 and 9-15 are found in aU subtypes, while the exons 4-8 appear in various combinations, allowing 32 possible combinations. Exon 16 or 17 are found in every subtype. Altogether, 64 different mRNAs can be formed from the troponin pre-mRNA. After Breitbart and Nadal-Grinard (1986). b) Tropomyosin is a muscle protein that can be alternatively spliced in different muscle tissue. Shown in the figure are the predominant subtypes for striated and smooth muscle. After Wieczorek et al., 1989.

Other nonhistone nuclear proteins. Polyacrylamide gel electrophoresis revealed more than 450 components in HeLa cell nuclei. Most are present in small amounts of <10,000 molecules per cell and are not detectable in cytoplasm.112 Among the more acidic proteins are many enzymes including RNA polymerases. There are also gene repressors, hormone-binding proteins, protein kinases, and topoi-somerases.113 Among the six most abundant nonhistone nuclear proteins in the rat are the cytoskeletal proteins myosin, actin, tubulin, and tropomyosin.114... 

The possibilities for alternative splicing are enormous. One particularly elaborate example is seen in the gene for tropomyosin in vertebrates. Recall that tropomyosin is a key component of vertebrate striated muscle (see fig. 5.18). The mRNA for tropomyosin found in striated muscle undergoes nine splices in the process of maturation (fig. 31.22). Variants of tropomyosin resulting from alternative splicing are found in other tissues of the same organism. It seems likely... 

One family with CCD arising from an RyRl mutation also had nemaline rods similar to those found with nemaline myopathies (NM) (Scacheri 2000). Muscle fibers from these patients show frequent clusters of rod-like structures. The autosomal dominant form of NM has been linked to mutations in the genes for a-tropomyosin and skeletal a-actin. A recessive form is associated with mutations in nebulin and a-tropomyosin. A major, unanswered question is whether and/or how a mutation in RyRl can produce a similar pathology. 

The contractile proteins of the myofibril include three troponin regulatory proteins. The troponin complex includes three protein subunits, troponin C (the calcium-binding component), troponin I (the inhibitory component), and troponin T (the tropomyosin-binding component). The subunits exist in a number of isoforms. The distribution of these isoforms varies between cardiac muscle and slow- and fast-twitch skeletal muscle. Only two major isoforms of troponin C are found in human heart and skeletal muscle. These are characteristic of slow- and fast-twitch skeletal muscle. The heart isoform is identical with the slow-twitch skeletal muscle isoform. Isoforms of cardiac-specific troponin T (cTnT) and cTnl also have been identified and are the products of unique genes. All cardiac troponins are localized primarily in the myofibrils (94%-97%), with a smaller cytoplasm fraction (3%-6%). 

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