Regulation of Myofibrillar Protein Gene Expression

Abstract

The contraction of skeletal and cardiac muscle is the result of a physiological conversion of chemical energy into mechanical energy, which takes place in a highly ordered three dimensional matrix of myofibrillar proteins. The basic unit of the contractile process in striated muscle is the sarcomere (Squire, 1981), which is composed of thick and thin filaments tandemly arranged in the myofibril. The sarcomere is composed of 10–15 myofibrillar proteins, but of these only myosin, actin, troponin, and tropomyosin participate directly in the contractile event. Regulation of expression of the myofibrillar protein genes seems to occur at the transcriptional level, with some of their RNA products exhibiting alternative exon splicing in the generation of multiple protein isoforms. Some of these primary RNA transcripts are also generated by differential initiation at alternate promoters (Nabeshima et al., 1984; Periasamy et al., 1984a; Robert et al., 1984). Muscle protein diversity can further be manifested by termination of primary transcripts at alternative 3’ untranslated sequences (Basi et al., 1984; Ruiz-Opazo et al., 1985; Bernstein et al., 1986; Rozek and Davidson, 1986). Generation of different protein forms by alternative splicing of identical primary RNA transcripts must involve trans-acting factors, some of which are tissue specific (Nadal-Ginard et al., 1987). A cis-acting factor refers to a DNA locus that affects the activity of DNA sequences on its own molecule of DNA, whereas a trans-acting factor refers to a diffusible product able to act on all receptive sites in the cell.