prpf4 is essential for cell survival and posterior lateral line primordium migration in zebrafish

State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China

More Information

Corresponding author: E-mail address: jiasj@mail.tsinghua.edu.cn (Shunji Jia)

These authors contributed equally to this work.

摘要

- /
- /
- /
Abstract: Prpf4 (pre-mRNA processing factor 4), a key component of spliceosome, plays critical roles in pre-mRNA splicing and its mutations result in retinitis pigmentosa due to photoreceptor defects. In this study, we characterized a zebrafish prpf4 mutant harboring a Tol2 transposon-based gene trap cassette in the third intron of the prpf4 gene. Cells in the brain and spinal cord gradually undergo p53-dependent apoptosis after 28 hpf in prpf4 mutants, suggesting that a widespread function of prpf4 in neural cell survival. In addition, prpf4 is essential for survival of posterior lateral line primordial (pLLP) cells. prpf4 deficiency perturbs Fgf, Wnt/β-catenin and chemokine signaling pathways and impairs pLLP migration. RNA-Seq analysis suggests that prpf4 deficiency may impair spliceosome assembly, leading to compensatory upregulation of core spliceosomal genes and alteration of pre-mRNA splicing. Taken together, our studies uncover an essential role of prpf4 in pre-mRNA splicing, cell survival and pLLP migration.
- Splicing /
- Apoptosis /
- pLLP /
- Zebrafish
These authors contributed equally to this work.
注释:

HTML全文

参考文献(41)

[1]	Aman, A., Nguyen, M., Piotrowski, T. Wnt/beta-catenin dependent cell proliferation underlies segmented lateral line morphogenesis Dev. Biol., 349 (2011),pp. 470-482
[2]	Aman, A., Piotrowski, T. Wnt/beta-catenin and Fgf signaling control collective cell migration by restricting chemokine receptor expression Dev. Cell, 15 (2008),pp. 749-761
[3]	Berghmans, S., Murphey, R.D., Wienholds, E. et al. Proc. Natl. Acad. Sci. U. S. A., 102 (2005),pp. 407-412
[4]	Chan, J.Y., Chen, Y.C., Liu, S.T. et al. Characterization of a new mouse p53 variant: loss-of-function and gain-of-function J. Biomed. Sci., 21 (2014),p. 40
[5]	Chen, X., Liu, Y., Sheng, X. et al. Hum. Mol. Genet., 23 (2014),pp. 2926-2939
[6]	Chitramuthu, B.P., Bennett, H.P. J. Vis. Exp. (2013)
[7]	Culbertson, M.R., Neeno-Eckwall, E. RNA, 11 (2005),pp. 1333-1339
[8]	Dalle Nogare, D., Somers, K., Rao, S. et al. Leading and trailing cells cooperate in collective migration of the zebrafish posterior lateral line primordium Development, 141 (2014),pp. 3188-3196
[9]	Dona, E., Barry, J.D., Valentin, G. et al. Directional tissue migration through a self-generated chemokine gradient Nature, 503 (2013),pp. 285-289
[10]	Ghosh, A., Stewart, D., Matlashewski, G. Regulation of human p53 activity and cell localization by alternative splicing Mol. Cell Biol., 24 (2004),pp. 7987-7997
[11]	Gompel, N., Cubedo, N., Thisse, C. et al. Pattern formation in the lateral line of zebrafish Mech. Dev., 105 (2001),pp. 69-77
[12]	Han, X., Wei, Y., Wang, H. et al. Nonsense-mediated mRNA decay: a 'nonsense' pathway makes sense in stem cell biology Nucleic Acids Res., 46 (2018),pp. 1038-1051
[13]	Han, Y., Mu, Y., Li, X. et al. Grhl2 deficiency impairs otic development and hearing ability in a zebrafish model of the progressive dominant hearing loss DFNA28 Hum. Mol. Genet., 20 (2011),pp. 3213-3226
[14]	Horowitz, D.S., Kobayashi, R., Krainer, A.R. A new cyclophilin and the human homologues of yeast Prp3 and Prp4 form a complex associated with U4/U6 snRNPs RNA, 3 (1997),pp. 1374-1387
[15]	Huang da, W., Sherman, B.T., Lempicki, R.A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources Nat. Protoc., 4 (2009),pp. 44-57
[16]	Lecaudey, V., Cakan-Akdogan, G., Norton, W.H. et al. Dynamic Fgf signaling couples morphogenesis and migration in the zebrafish lateral line primordium Development, 135 (2008),pp. 2695-2705
[17]	Lei, L., Yan, S.Y., Yang, R. et al. Spliceosomal protein eftud2 mutation leads to p53-dependent apoptosis in zebrafish neural progenitors Nucleic Acids Res., 45 (2017),pp. 3422-3436
[18]	Lerner, M.R., Steitz, J.A. Antibodies to small nuclear RNAs complexed with proteins are produced by patients with systemic lupus erythematosus Proc. Natl. Acad. Sci. U. S. A., 76 (1979),pp. 5495-5499
[19]	Linder, B., Dill, H., Hirmer, A. et al. Systemic splicing factor deficiency causes tissue-specific defects: a zebrafish model for retinitis pigmentosa Hum. Mol. Genet., 20 (2011),pp. 368-377
[20]	Linder, B., Hirmer, A., Gal, A. et al. Identification of a PRPF4 loss-of-function variant that abrogates U4/U6.U5 tri-snRNP integration and is associated with retinitis pigmentosa PLoS One, 9 (2014)
[21]	Luker, K.E., Steele, J.M., Mihalko, L.A. et al. Constitutive and chemokine-dependent internalization and recycling of CXCR7 in breast cancer cells to degrade chemokine ligands Oncogene, 29 (2010),pp. 4599-4610
[22]	Metcalfe, W.K. Sensory neuron growth cones comigrate with posterior lateral line primordial cells in zebrafish J. Comp. Neurol., 238 (1985),pp. 218-224
[23]	Pasternack, S.M., Refke, M., Paknia, E. et al. Am. J. Hum. Genet., 92 (2013),pp. 81-87
[24]	Patel, A.A., Steitz, J.A. Splicing double: insights from the second spliceosome Nat. Rev. Mol. Cell Biol., 4 (2003),pp. 960-970
[25]	Robinson, M.D., McCarthy, D.J., Smyth, G.K. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data Bioinformatics, 26 (2010),pp. 139-140
[26]	Schweingruber, C., Rufener, S.C., Zund, D. et al. Nonsense-mediated mRNA decay - mechanisms of substrate mRNA recognition and degradation in mammalian cells Biochim. Biophys. Acta, 1829 (2013),pp. 612-623
[27]	Schwerk, C., Schulze-Osthoff, K. Regulation of apoptosis by alternative pre-mRNA splicing Mol. Cell, 19 (2005),pp. 1-13
[28]	Shen, S., Park, J.W., Lu, Z.X. et al. rMATS: robust and flexible detection of differential alternative splicing from replicate RNA-Seq data Proc. Natl. Acad. Sci. U. S. A., 111 (2014),pp. E5593-E5601
[29]	Tanackovic, G., Ransijn, A., Ayuso, C. et al. Am. J. Hum. Genet., 88 (2011),pp. 643-649
[30]	Tanackovic, G., Ransijn, A., Thibault, P. et al. Hum. Mol. Genet., 20 (2011),pp. 2116-2130
[31]	Tarn, W.Y., Steitz, J.A. Pre-mRNA splicing: the discovery of a new spliceosome doubles the challenge Trends Biochem. Sci., 22 (1997),pp. 132-137
[32]	Thisse, C., Thisse, B. Nat. Protoc., 3 (2008),pp. 59-69
[33]	Tokheim, C., Park, J.W., Xing, Y. PrimerSeq: design and visualization of RT-PCR primers for alternative splicing using RNA-seq data Dev. Reprod. Biol., 12 (2014),pp. 105-109
[34]	Trapnell, C., Pachter, L., Salzberg, S.L. TopHat: discovering splice junctions with RNA-Seq Bioinformatics, 25 (2009),pp. 1105-1111
[35]	Valentin, G., Haas, P., Gilmour, D. The chemokine SDF1a coordinates tissue migration through the spatially restricted activation of Cxcr7 and Cxcr4b Curr. Biol., 17 (2007),pp. 1026-1031
[36]	Wu, Q., Krainer, A.R. Splicing of a divergent subclass of AT-AC introns requires the major spliceosomal snRNAs RNA, 3 (1997),pp. 586-601
[37]	Xing, C., Gong, B., Xue, Y. et al. TGFbeta1a regulates zebrafish posterior lateral line formation via Smad5 mediated pathway J. Mol. Cell Biol., 7 (2015),pp. 48-61
[38]	Xiong, C., Liu, X., Meng, A. The kinase activity-deficient isoform of the protein araf antagonizes Ras/mitogen-activated protein kinase (Ras/MAPK) signaling in the zebrafish embryo J. Biol. Chem., 290 (2015),pp. 25512-25521
[39]	Yu, Y., Chi, B., Xia, W. et al. U1 snRNP is mislocalized in ALS patient fibroblasts bearing NLS mutations in FUS and is required for motor neuron outgrowth in zebrafish Nucleic Acids Res., 43 (2015),pp. 3208-3218
[40]	Zhao, X., Zhao, L., Tian, T. et al. Interruption of cenph causes mitotic failure and embryonic death, and its haploinsufficiency suppresses cancer in zebrafish J. Biol. Chem., 285 (2010),pp. 27924-27934
[41]	Zheng, X., Yang, S., Han, Y. et al. Loss of zygotic NUP107 protein causes missing of pharyngeal skeleton and other tissue defects with impaired nuclear pore function in zebrafish embryos J. Biol. Chem., 287 (2012),pp. 38254-38264