Zebrafish study links minor spliceosome component U4atac to cilium formation via tmem107l and rfx7b splicing

A preprint posted to bioRxiv on 20 August 2026 reports that u4atac — the zebrafish orthologue of the human minor spliceosome component encoded by RNU4ATAC — regulates the development of primary cilia in the embryonic brain through its control of minor intron splicing in tmem107l and rfx7b.

In humans, bi-allelic pathogenic variants in RNU4ATAC cause Roifman syndrome and MOPD1/Taybi-Linder syndrome, characterised by microcephaly, growth retardation, skeletal dysplasia, and immunodeficiency. The minor spliceosome — of which U4atac snRNA is a core component — is responsible for splicing the approximately 700 U12-type (minor) introns in the human genome, which represent less than 1% of all introns but are enriched in genes involved in cell division, differentiation, and DNA repair.

The researchers used zebrafish models with disrupted u4atac function and demonstrated defective cilium biogenesis in brain cells, phenocopying features of ciliopathy syndromes. By examining splicing of specific U12-type introns, they identified tmem107l and rfx7b — both encoding proteins with established roles in ciliogenesis — as downstream mediators of this effect.

The findings extend the mechanistic understanding of RNU4ATAC-associated disorders and suggest an underappreciated overlap between minor spliceopathy and ciliopathy, two previously considered distinct categories of rare genetic disease. The authors note that their team had previously identified patients with RNU4ATAC bi-allelic variants presenting with atypical Joubert syndrome features, a recognised ciliopathy.

This is a preprint and has not yet been peer-reviewed.