Functional domains of the Drosophila melanogaster muscle myosin heavy-chain gene are encoded by alternatively spliced exons.

Abstract

The single-copy Drosophila muscle myosin heavy-chain (MHC) gene, located at 36B(2L), has a complex exon structure that produces a diversity of larval and adult muscle MHC isoforms through regulated alternative RNA splicing. Genomic and cDNA sequence analyses revealed that this 21-kilobase MHC gene encodes these MHC isoforms in 19 exons. However, five sets of these exons, encoding portions of the S1 head and the hinge domains of the MHC protein, are tandemly repeated as two, three, four, or five divergent copies, which are individually spliced into RNA transcripts. RNA hybridization studies with exon-specific probes showed that at least 10 of the 480 possible MHC isoforms that could arise by alternative RNA splicing of these exons are expressed as MHC transcripts and that the expression of specific members of alternative exon sets is regulated, both in stage and in muscle-type specificity. This regulated expression of specific exons is of particular interest because the alternatively spliced exon sets encode discrete domains of the MHC protein that likely contribute to the specialized contractile activities of different Drosophila muscle types. The alternative exon structure of the Drosophila MHC gene and the single-copy nature of this gene in the Drosophila genome make possible transgenic experiments to test the physiological functions of specific MHC protein domains and genetic and molecular experiments to investigate the mechanisms that regulate alternative exon splicing of MHC and other muscle gene transcripts.