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.
- 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.
- MeSH Terms
- DEAD-box RNA Helicases/genetics*
- DEAD-box RNA Helicases/metabolism*
- Genes, Lethal
- Organ Specificity/genetics
- RNA-Binding Proteins/genetics*
- RNA-Binding Proteins/metabolism*
- Ribonucleoprotein, U4-U6 Small Nuclear/genetics
- Ribonucleoprotein, U4-U6 Small Nuclear/metabolism
- Thymus Gland/abnormalities
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism*
- 17416673 Full text @ Proc. Natl. Acad. Sci. USA
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. (2007) Network of coregulated spliceosome components revealed by zebrafish mutant in recycling factor p110. Proceedings of the National Academy of Sciences of the United States of America. 104(16):6608-6613.
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.
Genes / Markers
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes