Yanchao Han
Pengfei Xu
Shihui Ding
Guangyuan Li
Hongbin Jin
Yaping Meng
Anming Meng
Shunji Jia
State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China
More InformationCorresponding author: E-mail address: jiasj@mail.tsinghua.edu.cn (Shunji Jia)
Received Date: 2018-01-24
Accepted Date:2018-05-17
Rev Recd Date:2018-04-20
Available Online: 2018-08-07 Publish Date:2018-08-20
Abstract
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.Keywords: Splicing,
Apoptosis,
pLLP,
Zebrafish
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