生物
RNA剪接
斑马鱼
细胞生物学
内含子
Wnt信号通路
剪接体
外显子
选择性拼接
遗传学
基因
核糖核酸
信号转导
作者
Yixia Wang,Yanchao Han,Pengfei Xu,Shihui Ding,Guangyuan Li,Hongbin Jin,Yahui Meng,Anming Meng,Shaofeng Jia
标识
DOI:10.1016/j.jgg.2018.05.008
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 prpf4t243 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 prpf4t243 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.
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