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| Status |
Public on Jan 06, 2021 |
| Title |
Prpf31 is essential for the survival and differentiation of retinal progenitor cells by modulating alternative splicing |
| Organism |
Danio rerio |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Dysfunction of splicing factors often result in abnormal cell differentiation and apoptosis, especially in neural tissues. Mutations in pre-mRNAs processing factor 31 (PRPF31) cause autosomal dominant retinitis pigmentosa, a progressive retinal degeneration disease. The transcriptome-wide splicing events specifically regulated by PRPF31 and their biological roles in the development and maintenance of retina are still unclear. Here, we showed that the differentiation and viability of retinal progenitor cells (RPCs) are severely perturbed in prpf31 knockout zebrafish when compared with other tissues at an early embryonic stage. At the cellular level, significant mitotic arrest and DNA damage were observed. These defects could be rescued by the wild-type human PRPF31 rather than the disease-associated mutants. Further bioinformatic analysis and experimental verification uncovered that Prpf31 deletion predominantly causes the skipping of exons with a weak 5′ splicing site. Moreover, genes necessary for DNA repair and mitotic progression are most enriched among the differentially spliced events, which may explain the cellular and tissular defects in prpf31 mutant retinas. This is the first time that Prpf31 is demonstrated to be essential for the survival and differentiation of RPCs during retinal neurogenesis by specifically modulating the alternative splicing of genes involved in DNA repair and mitosis.
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| Overall design |
Head mRNA profiles of 36 hpf sibling (wild type) and prpf31-/- zebrafish were generated by deep sequence in three independent biological replicates.
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| Contributor(s) |
Li J, Liu F, Lv Y, Sun K, Zhao Y, Reilly J, Zhang Y, Yu S, Tu J, Liu X, Qin Y, Huang Y, Gao P, Jia D, Chen X, Han Y, Shu X, Luo D, Tang Z, Liu M |
| Citation(s) |
33476374 |
| Submission date |
May 27, 2020 |
| Last update date |
Mar 10, 2021 |
| Contact name |
Jingzhen Li |
| E-mail(s) |
abc12314156@sina.com
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| Organization name |
Huazhong University of Science and Technology
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| Street address |
Wuhan, Hubei 430074, PR China
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| City |
Wuhan |
| ZIP/Postal code |
430074 |
| Country |
China |
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| Platforms (1) |
| GPL14875 |
Illumina HiSeq 2000 (Danio rerio) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA635369 |
| SRA |
SRP264942 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE151273_fpkm.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
| GSE151273_readcount.txt.gz |
442.8 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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