PerspectiveGenetics

Minor Splicing, Disrupted

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Science  08 Apr 2011:
Vol. 332, Issue 6026, pp. 184-185
DOI: 10.1126/science.1205503

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Summary

The excision of noncoding intron sequences from primary transcripts, also called mRNA splicing, is a central step in eukaryotic gene expression. This process is necessary for producing functional mRNA molecules and thus for the viability of cells and organisms. Although many disease-associated mutations affect splicing factors or the sites where splicing occurs, only a few mutations have been identified in the core components of the spliceosome, an RNA-protein complex that carries out splicing. These mutations occur in the protein constituents of the spliceosome (1). On pages 238 and 240 of this issue, He et al. (2) and Edery et al. (3) identify human disease-causing mutations in a gene that encodes a small nuclear RNA (snRNA) constituent of the spliceosome. These mutations in the U4atac snRNA are associated with microcephalic osteodysplastic primordial dwarfism type I (MOPD I), also known as Taybi-Linder syndrome (TALS). This rare disorder causes severe intrauterine and postnatal growth retardation, multiple developmental defects in various organs, and death within 3 years after birth. The findings provide important genetic tools for diagnosing the disease and for counseling mutation carriers in affected families, but also have implications for understanding splicing diseases in general.