PUBLICATION
The splicing factor DHX38 enables retinal development through safeguarding genome integrity
- Authors
- Sun, K., Han, Y., Li, J., Yu, S., Huang, Y., Zhang, Y., Reilly, J., Tu, J., Gao, P., Jia, D., Chen, X., Hu, H., Ren, M., Li, P., Luo, J., Ren, X., Zhang, X., Shu, X., Liu, F., Liu, M., Tang, Z.
- ID
- ZDB-PUB-231023-60
- Date
- 2023
- Source
- iScience 26: 108103108103 (Journal)
- Registered Authors
- Huang, Yuwen, Li, Jingzhen, Liu, Fei, Liu, Mugen, Yu, Shanshan, Zhang, Xianqin
- Keywords
- Developmental genetics, Molecular physiology
- MeSH Terms
- none
- PubMed
- 37867960 Full text @ iScience
Citation
Sun, K., Han, Y., Li, J., Yu, S., Huang, Y., Zhang, Y., Reilly, J., Tu, J., Gao, P., Jia, D., Chen, X., Hu, H., Ren, M., Li, P., Luo, J., Ren, X., Zhang, X., Shu, X., Liu, F., Liu, M., Tang, Z. (2023) The splicing factor DHX38 enables retinal development through safeguarding genome integrity. iScience. 26:108103108103.
Abstract
DEAH-Box Helicase 38 (DHX38) is a pre-mRNA splicing factor and also a disease-causing gene of autosomal recessive retinitis pigmentosa (arRP). The role of DHX38 in the development and maintenance of the retina remains largely unknown. In this study, by using the dhx38 knockout zebrafish model, we demonstrated that Dhx38 deficiency causes severe differentiation defects and apoptosis of retinal progenitor cells (RPCs) through disrupted mitosis and increased DNA damage. Furthermore, we found a significant accumulation of R-loops in the dhx38-deficient RPCs and human cell lines. Finally, we found that DNA replication stress is the prerequisite for R-loop-induced DNA damage in the DHX38 knockdown cells. Taken together, our study demonstrates a necessary role of DHX38 in the development of retina and reveals a DHX38/R-loop/replication stress/DNA damage regulatory axis that is relatively independent of the known functions of DHX38 in mitosis control.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping