Association of TALS developmental disorder with defect in minor splicing component U4atac snRNA

Science. 2011 Apr 8;332(6026):240-3. doi: 10.1126/science.1202205.


The spliceosome, a ribonucleoprotein complex that includes proteins and small nuclear RNAs (snRNAs), catalyzes RNA splicing through intron excision and exon ligation to produce mature messenger RNAs, which, in turn serve as templates for protein translation. We identified four point mutations in the U4atac snRNA component of the minor spliceosome in patients with brain and bone malformations and unexplained postnatal death [microcephalic osteodysplastic primordial dwarfism type 1 (MOPD 1) or Taybi-Linder syndrome (TALS); Mendelian Inheritance in Man ID no. 210710]. Expression of a subgroup of genes, possibly linked to the disease phenotype, and minor intron splicing were affected in cell lines derived from TALS patients. Our findings demonstrate a crucial role of the minor spliceosome component U4atac snRNA in early human development and postnatal survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Pairing
  • Cell Line
  • Child, Preschool
  • Chromosomes, Human, Pair 2 / genetics
  • Dwarfism / genetics
  • Dwarfism / metabolism
  • Female
  • Fetal Growth Retardation / genetics
  • Fetal Growth Retardation / metabolism
  • Humans
  • Infant
  • Introns
  • Inverted Repeat Sequences
  • Male
  • Microcephaly / genetics
  • Microcephaly / metabolism
  • Microtubule-Associated Proteins / genetics
  • Nucleic Acid Conformation
  • Osteochondrodysplasias / genetics
  • Osteochondrodysplasias / metabolism
  • Pedigree
  • Point Mutation*
  • RNA Splice Sites
  • RNA Splicing*
  • RNA, Small Nuclear / chemistry
  • RNA, Small Nuclear / genetics*
  • RNA, Small Nuclear / metabolism
  • Spliceosomes / genetics*
  • Spliceosomes / metabolism


  • CLASP1 protein, human
  • Microtubule-Associated Proteins
  • RNA Splice Sites
  • RNA, Small Nuclear
  • U12 small nuclear RNA
  • U4 small nuclear RNA
  • U6 small nuclear RNA

Supplementary concepts

  • Microcephalic osteodysplastic primordial dwarfism, type 1