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
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
Figures
Figure Gallery (5 images)
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
hzu20
    		Small Deletion
    knu3TgTransgenic Insertion
      nl1TgTransgenic Insertion
        zdf1
          		Point Mutation
          1 - 4 of 4
          Show
          Human Disease / Model
          No data available
          Sequence Targeting Reagents
          Target Reagent Reagent Type
          dhx38CRISPR1-dhx38CRISPR
          1 - 1 of 1
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          Fish
          No data available
          Antibodies
          Orthology
          No data available
          Engineered Foreign Genes
          Marker Marker Type Name
          EGFPEFGEGFP
          1 - 1 of 1
          Show
          Mapping
          No data available
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          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.