ZFIN ID: ZDB-PUB-070413-2
Network of coregulated spliceosome components revealed by zebrafish mutant in recycling factor p110
Trede, N.S., Medenbach, J., Damianov, A., Hung, L.H., Weber, G.J., Paw, B.H., Zhou, Y., Hersey, C., Zapata, A., Keefe, M., Barut, B.A., Stuart, A.B., Katz, T., Amemiya, C.T., Zon, L.I., and Bindereif, A.
Date: 2007
Source: Proceedings of the National Academy of Sciences of the United States of America   104(16): 6608-6613 (Journal)
Registered Authors: Amemiya, Chris, Barut, Bruce, Hersey, Candace, Keefe, Matthew, Paw, Barry, Stuart, Andrew, Trede, Nick, Weber, Gerhard, Zhou, Yi, Zon, Leonard I.
Keywords: none
Microarrays: GEO:GSE5586
MeSH Terms:
  • Animals
  • DEAD-box RNA Helicases/genetics*
  • DEAD-box RNA Helicases/metabolism*
  • Genes, Lethal
  • Mutagenesis
  • Organ Specificity/genetics
  • Phenotype
  • RNA-Binding Proteins/genetics*
  • RNA-Binding Proteins/metabolism*
  • Ribonucleoprotein, U4-U6 Small Nuclear/genetics
  • Ribonucleoprotein, U4-U6 Small Nuclear/metabolism
  • Spliceosomes/physiology*
  • Thymus Gland/abnormalities
  • Zebrafish*/genetics
  • Zebrafish*/metabolism
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism*
PubMed: 17416673 Full text @ Proc. Natl. Acad. Sci. USA
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.