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

被引:6
作者
Wang, Yixia [1 ]
Han, Yanchao [1 ]
Xu, Pengfei [1 ]
Ding, Shihui [1 ]
Li, Guangyuan [1 ]
Jin, Hongbin [1 ]
Meng, Yaping [1 ]
Meng, Anming [1 ]
Jia, Shunji [1 ]
机构
[1] Tsinghua Univ, Sch Life Sci, Tsinghua Peking Ctr Life Sci, State Key Lab Membrane Biol, Beijing 100084, Peoples R China
基金
中国国家自然科学基金;
关键词
prpf4; Splicing; Apoptosis; pLLP; Zebrafish; MESSENGER-RNA DECAY; DOMINANT RETINITIS-PIGMENTOSA; TISSUE MIGRATION; SEQ DATA; SPLICEOSOME; MUTATIONS; PROTEIN; EXPRESSION; APOPTOSIS; DEFECTS;
D O I
10.1016/j.jgg.2018.05.008
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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(t243) mutant harboring a To12 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(t243) 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/beta-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. Copyright (C) 2018, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Limited and Science Press. All rights reserved.
引用
收藏
页码:443 / 453
页数:11
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