What is the extent of tropomyosin isoform diversity?
Three of the tropomyosin genes can choose between two alternative promoters (1a and 1b), two alternative exons (6a and 6b), and four carboxyl-terminal exons (9a, 9b, 9c, and 9d). In the case of the Tm5 gene, one muscle isoform, -Tms, 21 and four non-muscle isoforms, termed Tm5 NM1 to NM4,22 were known to be generated from this gene (Figure 1). By systematic reverse transcription polymerase chain reaction (RT-PCR) amplification using primers specific for each alternative exon, it has been shown that five different splice combinations were possible for alternative carboxyl-terminal exon 9: 9a + 9b, 9a + 9c, 9a + 9d, 9c, and 9d, and that each of these combinations existed with both internal exon 6a and 6b.20 This gives rise to at least 10 isoforms: NM 1–10 (Figure 1). The novel splicing combination 9a + 9d results in a translational termination signal in the first codon of exon 9d which leaves it as a long 3′ untranslated region (3′ UTR; NM 5, 6), like exon 9b which provides only the 3′ U