Network of coregulated spliceosome components revealed by zebrafish mutant in recycling factor p110.
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.
Trede
Nikolaus S
NS
Institute of Biochemistry, Justus-Liebig-University, D-35392 Giessen, Germany.
Medenbach
Jan
J
Damianov
Andrey
A
Hung
Lee-Hsueh
LH
Weber
Gerhard J
GJ
Paw
Barry H
BH
Zhou
Yi
Y
Hersey
Candace
C
Zapata
Agustin
A
Keefe
Matthew
M
Barut
Bruce A
BA
Stuart
Andrew B
AB
Katz
Tammisty
T
Amemiya
Chris T
CT
Zon
Leonard I
LI
Bindereif
Albrecht
A
D000818:Animals; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000378:metabolism*; D005804:Genes, Lethal; D016296:Mutagenesis; D009928:Organ Specificity / Q000235:genetics; D010641:Phenotype; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D017414:Ribonucleoprotein, U4-U6 Small Nuclear / Q000235:genetics / Q000378:metabolism; D017381:Spliceosomes / Q000502:physiology*; D013950:Thymus Gland / Q000002:abnormalities; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism*
D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; D017414:Ribonucleoprotein, U4-U6 Small Nuclear; D029961:Zebrafish Proteins; C519855:SART3 protein, zebrafish; D053487:DEAD-box RNA Helicases