Network of Coregulated Spliceosome Components Revealed by Zebrafish Mutant in Recycling Factor P110

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2007 Apr 10

PMID 17416673

Citations 43

Authors

Nikolaus S Trede

Jan Medenbach

Andrey Damianov

Lee-Hsueh Hung

Gerhard J Weber

Barry H Paw

Yi Zhou

Candace Hersey

Agustin Zapata

Matthew Keefe

Bruce A Barut

Andrew B Stuart

Tammisty Katz

Chris T Amemiya

Leonard I Zon

Albrecht Bindereif

Affiliations

Soon will be listed here.

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.

Citing Articles

Interaction between RNF4 and SART3 is associated with the risk of schizophrenia.

Cheng Y, Chen X, Zhang X, Ju P, Wang W, Fang Y Heliyon. 2024; 10(12):e32743.

PMID: 38975171 PMC: 11226853. DOI: 10.1016/j.heliyon.2024.e32743.

Variants in SART3 cause a spliceosomopathy characterised by failure of testis development and neuronal defects.

Ayers K, Eggers S, Rollo B, Smith K, Davidson N, Siddall N Nat Commun. 2023; 14(1):3403.

PMID: 37296101 PMC: 10256788. DOI: 10.1038/s41467-023-39040-0.

Zebrafish: A Relevant Genetic Model for Human Primary Immunodeficiency (PID) Disorders?.

Basheer F, Sertori R, Liongue C, Ward A Int J Mol Sci. 2023; 24(7).

PMID: 37047441 PMC: 10095346. DOI: 10.3390/ijms24076468.

Tip110/SART3-Mediated Regulation of NF-κB Activity by Targeting IκBα Stability Through USP15.

Timani K, Rezaei S, Whitmill A, Liu Y, He J Front Oncol. 2022; 12:843157.

PMID: 35530338 PMC: 9070983. DOI: 10.3389/fonc.2022.843157.

The spliceosome factor sart3 regulates hematopoietic stem/progenitor cell development in zebrafish through the p53 pathway.

Zhao Y, Wu M, Li J, Meng P, Chen J, Huang Z Cell Death Dis. 2021; 12(10):906.

PMID: 34611130 PMC: 8492694. DOI: 10.1038/s41419-021-04215-4.

References

Trede N, Zapata A, Zon L . Fishing for lymphoid genes. Trends Immunol. 2001; 22(6):302-7. DOI: 10.1016/s1471-4906(01)01939-1. View

Thisse B, Heyer V, Lux A, Alunni V, Degrave A, Seiliez I . Spatial and temporal expression of the zebrafish genome by large-scale in situ hybridization screening. Methods Cell Biol. 2004; 77:505-19. DOI: 10.1016/s0091-679x(04)77027-2. View

Vithana E, Abu-Safieh L, Allen M, Carey A, Papaioannou M, Chakarova C . A human homolog of yeast pre-mRNA splicing gene, PRP31, underlies autosomal dominant retinitis pigmentosa on chromosome 19q13.4 (RP11). Mol Cell. 2001; 8(2):375-81. DOI: 10.1016/s1097-2765(01)00305-7. View

Chakarova C, Hims M, Bolz H, Abu-Safieh L, Patel R, Papaioannou M . Mutations in HPRP3, a third member of pre-mRNA splicing factor genes, implicated in autosomal dominant retinitis pigmentosa. Hum Mol Genet. 2002; 11(1):87-92. DOI: 10.1093/hmg/11.1.87. View

Bell M, Schreiner S, Damianov A, Reddy R, Bindereif A . p110, a novel human U6 snRNP protein and U4/U6 snRNP recycling factor. EMBO J. 2002; 21(11):2724-35. PMC: 126028. DOI: 10.1093/emboj/21.11.2724. View

Brow D . Allosteric cascade of spliceosome activation. Annu Rev Genet. 2002; 36:333-60. DOI: 10.1146/annurev.genet.36.043002.091635. View

Rader S, Guthrie C . A conserved Lsm-interaction motif in Prp24 required for efficient U4/U6 di-snRNP formation. RNA. 2002; 8(11):1378-92. PMC: 1370345. DOI: 10.1017/s1355838202020010. View

Faustino N, Cooper T . Pre-mRNA splicing and human disease. Genes Dev. 2003; 17(4):419-37. DOI: 10.1101/gad.1048803. View

Jurica M, Moore M . Pre-mRNA splicing: awash in a sea of proteins. Mol Cell. 2003; 12(1):5-14. DOI: 10.1016/s1097-2765(03)00270-3. View

10.

Traver D, Herbomel P, Patton E, Murphey R, Yoder J, Litman G . The zebrafish as a model organism to study development of the immune system. Adv Immunol. 2004; 81:253-330. View

11.

Damianov A, Schreiner S, Bindereif A . Recycling of the U12-type spliceosome requires p110, a component of the U6atac snRNP. Mol Cell Biol. 2004; 24(4):1700-8. PMC: 344176. DOI: 10.1128/MCB.24.4.1700-1708.2004. View

12.

Blackburn C, Manley N . Developing a new paradigm for thymus organogenesis. Nat Rev Immunol. 2004; 4(4):278-89. DOI: 10.1038/nri1331. View

13.

Medenbach J, Schreiner S, Liu S, Luhrmann R, Bindereif A . Human U4/U6 snRNP recycling factor p110: mutational analysis reveals the function of the tetratricopeptide repeat domain in recycling. Mol Cell Biol. 2004; 24(17):7392-401. PMC: 506986. DOI: 10.1128/MCB.24.17.7392-7401.2004. View

14.

Dignam J, Lebovitz R, Roeder R . Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983; 11(5):1475-89. PMC: 325809. DOI: 10.1093/nar/11.5.1475. View

15.

Lee K, Bindereif A, Green M . A small-scale procedure for preparation of nuclear extracts that support efficient transcription and pre-mRNA splicing. Gene Anal Tech. 1988; 5(2):22-31. DOI: 10.1016/0735-0651(88)90023-4. View

16.

Shannon K, Guthrie C . Suppressors of a U4 snRNA mutation define a novel U6 snRNP protein with RNA-binding motifs. Genes Dev. 1991; 5(5):773-85. DOI: 10.1101/gad.5.5.773. View

17.

Mullins M, Hammerschmidt M, Haffter P, Nusslein-Volhard C . Large-scale mutagenesis in the zebrafish: in search of genes controlling development in a vertebrate. Curr Biol. 1994; 4(3):189-202. DOI: 10.1016/s0960-9822(00)00048-8. View

18.

Johnson S, Africa D, Horne S, Postlethwait J . Half-tetrad analysis in zebrafish: mapping the ros mutation and the centromere of linkage group I. Genetics. 1995; 139(4):1727-35. PMC: 1206498. DOI: 10.1093/genetics/139.4.1727. View

19.

Haffter P, Granato M, Brand M, Mullins M, Hammerschmidt M, Kane D . The identification of genes with unique and essential functions in the development of the zebrafish, Danio rerio. Development. 1996; 123:1-36. DOI: 10.1242/dev.123.1.1. View

20.

Raghunathan P, Guthrie C . A spliceosomal recycling factor that reanneals U4 and U6 small nuclear ribonucleoprotein particles. Science. 1998; 279(5352):857-60. DOI: 10.1126/science.279.5352.857. View