Preprint identifies Amus/MePCE capping enzyme as essential for minor spliceosome stability and reveals cross-pathway splicing interactions

A preprint on bioRxiv describes a previously uncharacterised genetic condition in which both the major and minor splicing pathways are simultaneously impaired, arising from loss of the Amus protein in Drosophila — and its mammalian homologue MePCE — which functions as the methyltransferase responsible for capping the U6 small nuclear RNA (snRNA).

The major spliceosome, which removes more than 99% of human introns and uses U6 snRNA as its catalytic component, and the minor spliceosome, which processes the remaining approximately 1% of introns using the related U6atac snRNA, have conventionally been regarded as largely independent pathways. The authors report that Amus/MePCE is required for the stability of U6atac, so its loss preferentially disrupts minor-class intron processing. They further present evidence that this creates downstream effects on major-class splicing, supporting the view that the two pathways interact mechanistically rather than operating in strict parallel.

The findings have potential relevance to understanding a class of rare diseases caused by minor spliceosome dysfunction — including some forms of microcephalic osteodysplastic primordial dwarfism and Roifman syndrome — though the authors do not make direct clinical claims. The work is a preprint and has not yet been peer-reviewed.