MOLECULAR-ORGANIZATION AND ALTERNATIVE SPLICING IN ZIPPER, THE GENE THAT ENCODES THE DROSOPHILA NONMUSCLE MYOSIN-II HEAVY-CHAIN

Genomic sequence of the entire zipper gene, that encodes non-muscle my osin II heavy chain (MHC) in Drosophila melanogaster, reveals a new, d ifferentially spliced exon in this essential locus and identifies a mo lecular lesion that is responsible for a severe embryonic lethal zippe r allele. There are two alternative splices in the head domain. The fi rst is present in the 5' untranslated sequence which, when employed, p roduces an N-terminal extension of 45 amino acids (aa). This splicofor m produces a protein that is stable in flies but less prevalent than t he isoform that lacks the extension. The second alternative exon (40 a a) is close to the nucleotide binding pocket. The position, size and s equence of this exon is conserved in D. simulans and putative alternat ive exons of different size (7 to 16 aa) but identical position have b een reported for other myosins throughout phylogeny. The functional si gnificance of neither alternative splice is clear. Sequence analysis o f genomic DNA identifies the lesion responsible for zip(IIF107), one o f the original severe embryonic lethal zipper alleles. Our primary str uctural data confirm and correct our previous sequence of the cDNA, es tablish the spatial relationship between zipper and unzipped (the gene originally thought to have been disrupted in zipper mutations), and p rovide a high resolution template for the precise mapping of mutations . (C) 1996 Academic Press Limited