A minor class of pre-mRNA introns whose excision requires a spliceosome containing U11, U12, U4atac/U6atac, and U5 snRNPs has been identified in plants, insects, and vertebrates. We have characterized single loci that specify the U6atac and U12 snRNAs of Drosophila melanogaster. P element-mediated disruptions of the U6atac and U12 genes cause lethality during the third instar larval and embryonic stages, respectively, and are rescued by U6atac and U12 transgenes. The P element disruption of U6atac results in excision defects of U12-type introns from several transcripts including an alternative U12-dependent spliced isoform of prospero, a homeodomain protein required for CNS development. Thus, we demonstrate the requirement for the U12 spliceosome in the development of a metazoan organism.

Therapeutic, IV.