We propose to analyze the genetics, structure and regulation of the myosin heavy chain (MHC) gene of Drosophila melanogaster. Drosophila is unusual i n that it possesses a single MHC gene rather than a MHC multigene family. This gene produces multiple RNA transcripts in a developmentally regulated fashion and these transcripts encode at least two forms of the MHC protein. We plan to continue our analysis of the differences between these transcripts, as well as to analyze their tissue-specific accumulation. We will also investigate the mechanisms involved in stage-specific RNA processing by constructing MHC genes with mutations at their stage-specific splice junction and assaying RNA processing in vivo and in vitro. We will continue to study several MHC mutants in order to characterize their DNA, RNA, and protein defects. These mutations cause the loss of flight ability in the heterozygous state and are lethal when homozygous. We will be particularly interested in comparing the ultrastructural defects in flight muscle to those in other muscle types. We plan to isolate and characterize other mutations in the MHC gene, as well as to transform null mutants with in vitro mutagenized MHC genes, in order to determine which regions of the MHC gene and protein are important for the function of specific muscle types. We will determine whether the cloned MHC gene encodes non-muscle MHC, a common protein whose function is not clearly defined. Analysis of non-muscle MHC in an organism that is amenable to gene transformation and genetic manipulation should lead to a better understanding of the funciton of this protein.
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