IDENTIFICATION OF NOVEL ALTERNATIVELY SPLICED ISOFORMS OF THE TROPOMYOSIN-ENCODING GENE, TMNM, IN THE RAT COCHLEA

Analysis of a rat cochlear cDNA library for the expression of the non- muscle (nm) tropomyosin (TM)-encoding gene (TMnm), demonstrated that f our nm isoforms were present. These four TMnm variants are NM-1, NM-2, NM-3 and NM-4. Nucleotide (nt) sequencing revealed that all these iso forms expressed the nm exon 1b sequence, but varied in their usage of the alternatively spliced exons 6a and b and 9a/b and d, representing skeletal muscle (sk) (exons 6b and 9a/b) and nm (6a and 9d) sequences. A novel exon 9 (designated as exon 9c) was associated with the NM-4 i soform and was also found to be expressed in the cochlea. Comparisons of the nt and amino acid (aa) sequences demonstrated a high homology b etween rat, mouse and human sequences encoding the 'classical' nm isof orm, TM30nm, which is designated herein as NM-1. The rat NM-1 nt homol ogy with mouse and human sequences also included the 3' untranslated r egion. Homologies were found between aa sequences of the C termini of NM-1 and the TM alpha smooth muscle and TM beta nm isoforms, between t he sk sequence of NM-3 and the TM alpha and beta sk isoforms, and betw een the novel 9c sequence of NM-4 and the TM alpha brain-1 isoform. Th ese data predict that the nm isoforms share biochemical properties des cribed for the other TM isoforms.