Network of coregulated spliceosome components revealed by zebrafish mutant in recycling factor p110

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 104; no. 16; pp. 6608 - 6613
• Main Authors: Trede, Nikolaus S, Medenbach, Jan, Damianov, Andrey, Hung, Lee-Hsueh, Weber, Gerhard J, Paw, Barry H, Zhou, Yi, Hersey, Candace, Zapata, Agustin, Keefe, Matthew, Barut, Bruce A, Stuart, Andrew B, Katz, Tammisty, Amemiya, Chris T, Zon, Leonard I, Bindereif, Albrecht
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 17-04-2007; National Acad Sciences
• Subjects: Animals; Biological Sciences; Danio rerio; DEAD-box RNA Helicases - genetics; DEAD-box RNA Helicases - metabolism; Embryos; Endocrine system; Fish; Freshwater; Gene expression; Genes; Genes, Lethal; Genetic mutation; Genomics; Genotype & phenotype; Mutagenesis; Mutation; Organ Specificity - genetics; Phenotype; Proteins; Recycling; Ribonucleic acid; Ribonucleoprotein, U4-U6 Small Nuclear - genetics; Ribonucleoprotein, U4-U6 Small Nuclear - metabolism; RNA; RNA Splicing Factors; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Small nuclear ribonucleoproteins; Small nuclear RNA; Spliceosomes; Spliceosomes - physiology; Splicing; T lymphocytes; Thymus Gland - abnormalities; Zebrafish - genetics; Zebrafish - metabolism; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0701919104

The spliceosome cycle consists of assembly, catalysis, and recycling phases. Recycling of postspliceosomal U4 and U6 small nuclear ribonucleoproteins (snRNPs) requires p110/SART3, a general splicing factor. In this article, we report that the zebrafish earl grey (egy) mutation maps in the p110 gene and results in a phenotype characterized by thymus hypoplasia, other organ-specific defects, and death by 7 to 8 days postfertilization. U4/U6 snRNPs were disrupted in egy mutant embryos, demonstrating the importance of p110 for U4/U6 snRNP recycling in vivo. Surprisingly, expression profiling of the egy mutant revealed an extensive network of coordinately up-regulated components of the spliceosome cycle, providing a mechanism compensating for the recycling defect. Together, our data demonstrate that a mutation in a general splicing factor can lead to distinct defects in organ development and cause disease.