The U6 snRNA capping enzyme Amus/MePCE is required for the stability of U6atac and the processing of introns with features of both major and minor classes
Over 99% of the introns in humans are removed by the major spliceosome with the U6 snRNA as the catalytic component while the rest 1% by the minor spliceosome containing U6atac. Recent evidence supports mechanistic interactions between the two splicing pathways even though they have been considered as operating in parallel. Here we report a unique genetic condition in which both splicing pathways are partially impaired, and present evidence supporting inter-pathway interactions. We recently showed that the Drosophila Amus protein and its mammalian homolog MePCE serve as the methyltransferase of U6 and protect its stability. We show here that U6atac is greatly reduced under the same amus or mepce mutant backgrounds, suggesting Amus/MePCE serves the same protective function for U6atac. Interestingly, the processing of canonical minor introns is not significantly affected in the mutants, suggesting that a minimal amount of U6atac is sufficient for those reactions. In contrast, the splicing of a second class of minor spliceosome sensitive introns are inhibited. These introns harbor splice sites different from the minor consensus even though they interact favorably with the minor spliceosome as shown by others. Interestingly, most members of this class of minor-like introns are evolutionarily younger than their canonical counterparts, and our in-depth analysis of one such intron supports that some of them might be functionally neutral. Our study provides empirical evidence supporting the existence of a class of introns jointly regulated by the two splicing pathways, and revealing additional complexity in the functional evolution of minor splicing.