Transgene analysis proves mRNA trans-splicing at the complex mod(mdg4) locus Drosophila

The Drosophila BTB domain containing gene mod(mdg4) produces a large number of protein isoforms combining a common N-terminal region of 402 aa with di fferent C termini. We have deduced the genomic structure of this complex lo cus and found that at least seven of the mod(mdg4) isoforms are encoded on both of its antiparallel DNA strands, suggesting the generation of mature m RNAs by trans-splicing. In transgenic assays, we demonstrate the ability of Drosophila to produce mod(mdg4) mRNAs by trans-splicing of pre-mRNAs gener ated from transgenes inserted at distant chromosomal positions. Furthermore , evidence is presented for occurring of trans-splicing of mod(mdg4)-specif ic exons encoded by the parallel DNA strand. The mod(mdg4) locus represents a new type of comlpex gene structure in which genetic complexity is resolv ed by extensive trans-splicing, giving important implications for genome se quencing projects. Demonstration of naturally occurring trans-splicing in t he model organism Drosophila opens new experimental approaches toward an an alysis of the underlying mechanisms.