title: Network of coregulated spliceosome components revealed by zebrafish mutant in recycling factor p110.
abstract: 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.
authors.affiliation: Institute of Biochemistry, Justus-Liebig-University, D-35392 Giessen, Germany.
authors.forename: Nikolaus S
authors.initials: NS
authors.lastname: Trede
authors.forename: Jan
authors.initials: J
authors.lastname: Medenbach
authors.forename: Andrey
authors.initials: A
authors.lastname: Damianov
authors.forename: Lee-Hsueh
authors.initials: LH
authors.lastname: Hung
authors.forename: Gerhard J
authors.initials: GJ
authors.lastname: Weber
authors.forename: Barry H
authors.initials: BH
authors.lastname: Paw
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.forename: Candace
authors.initials: C
authors.lastname: Hersey
authors.forename: Agustin
authors.initials: A
authors.lastname: Zapata
authors.forename: Matthew
authors.initials: M
authors.lastname: Keefe
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Barut
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Stuart
authors.forename: Tammisty
authors.initials: T
authors.lastname: Katz
authors.forename: Chris T
authors.initials: CT
authors.lastname: Amemiya
authors.forename: Leonard I
authors.initials: LI
authors.lastname: Zon
authors.forename: Albrecht
authors.initials: A
authors.lastname: Bindereif
mesh_terms: 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*
chemical_list: 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