PUBLICATION
The splicing factor Prpf31 is required for hematopoietic stem and progenitor cell expansion during zebrafish embryogenesis
- Authors
- Lv, Y., Li, J., Yu, S., Zhang, Y., Hu, H., Sun, K., Jia, D., Han, Y., Tu, J., Huang, Y., Liu, X., Zhang, X., Gao, P., Chen, X., Shaw Williams, M.T., Tang, Z., Shu, X., Liu, M., Ren, X.
- ID
- ZDB-PUB-240222-23
- Date
- 2024
- Source
- The Journal of biological chemistry 300(3): 105772 (Journal)
- Registered Authors
- Huang, Yuwen, Li, Jingzhen, Liu, Mugen, Liu, Xiliang, Yu, Shanshan
- Keywords
- Pre-mRNA processing factor 31 (Prpf31), RNA alternative splicing, expansion, hematopoietic stem and progenitor cells (HSPCs), mitotic malformation, zebrafish
- Datasets
- GEO:GSE171661
- MeSH Terms
-
- Animals
- Embryonic Development
- Mutation
- RNA Precursors/metabolism
- RNA Splicing Factors*/metabolism
- Stem Cells/metabolism
- Zebrafish*/genetics
- Zebrafish*/growth & development
- Zebrafish*/metabolism
- Zebrafish Proteins*/metabolism
- PubMed
- 38382674 Full text @ J. Biol. Chem.
Citation
Lv, Y., Li, J., Yu, S., Zhang, Y., Hu, H., Sun, K., Jia, D., Han, Y., Tu, J., Huang, Y., Liu, X., Zhang, X., Gao, P., Chen, X., Shaw Williams, M.T., Tang, Z., Shu, X., Liu, M., Ren, X. (2024) The splicing factor Prpf31 is required for hematopoietic stem and progenitor cell expansion during zebrafish embryogenesis. The Journal of biological chemistry. 300(3):105772.
Abstract
Pre-mRNA splicing is a precise regulated process, and is crucial for system development and homeostasis maintenance. Mutations in spliceosomal components have been found in various hematopoietic malignancies (HMs), and have been considered as oncogenic derivers of HMs. However, the role of spliceosomal components in normal and malignant hematopoiesis remain largely unknown. Pre-mRNA processing factor 31 (PRPF31) is a constitutive spliceosomal component, which mutations are associated with autosomal dominant retinitis pigmentosa. PRPF31 was found to be mutated in several HMs, but the function of PRPF31 in normal hematopoiesis has not been explored. In our previous study, we generated a prpf31 knockout zebrafish line, and reported that Prpf31 regulates the survival and differentiation of retinal progenitor cells (RPCs) by modulating the alternative splicing of genes involved in mitosis and DNA repair. In this study, by using the prpf31 knockout zebrafish line, we discovered that prpf31 knockout zebrafish exhibited severe defects in hematopoietic stem and progenitor cell (HSPC) expansion and its sequentially differentiated lineages. Immunofluorescence results showed that Prpf31 deficient HSPCs underwent malformed mitosis and M phase arrest during HSPC expansion. Transcriptome analysis and experimental validations revealed that Prpf31 deficiency extensively perturbed the alternative splicing of mitosis-related genes. Collectively, our findings elucidate a previously undescribed role for Prpf31 in HSPC expansion, through regulating the alternative splicing of mitosis-related genes.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping