The spliceosome is a ribonucleoprotein complex containing small nuclear (sn) RNAs, which catalyzes RNA splicing through intron excision and exon ligation to produce mature mRNAs, templates for protein translation. No mutations in human snRNAs have been described in humans, or linked to diseases. We identified four point mutations in the U4atac snRNA component of the minor spliceosome in patients with severe brain malformations and unexplained postnatal death (Taybi- Linder syndrome, TALS or microcephalic osteodysplastic primordial dwarfism type 1, MOPD1, MIM 210710). Minor intron splicing and expression of a subgroup of genes, possibly linked to the disease phenotype, were affected in cell lines derived from TALS patients. Our findings demonstrate the crucial role of minor spliceosome component, U4atac snRNA, in human brain development and postnatal survival.
Patrick EDERY, CRNL/Tiger