Positive and negative intronic regulatory elements control muscle-specificalternative exon splicing of Drosophila myosin heavy chain transcripts

Alternative splicing of Drosophila muscle myosin heavy chain (MHC) transcri pts is precisely regulated to ensure the expression of specific MHC isoform s required for the distinctive contractile activities of physiologically sp ecialized muscles. We have used transgenic expression analysis in combinati on with mutagenesis to identify cis-regulatory sequences that are required for muscle-specific splicing of exon 11, which is encoded by five alternati ve exons that produce alternative "converter" domains in the MHC head. Here , we report the identification of three conserved intronic elements (CIE1, -2, and -3) that control splicing of exon 11e in the indirect flight muscle (IFM). Each of these CIE elements has a distinct function: CIE1 acts as a splice repressor, while CIE2 and CIE3 behave as splice enhancers. These CIE elements function in combination with a nonconsensus splice donor to direc t IFM-specific splicing of exon 11e. An additional cis-regulatory element t hat is essential in coordinating the muscle-specific splicing of other alte rnative the muscle-specific splicing of alternative exon 11s.