PUBLICATION
Triclosan regulates alternative splicing events of nerve-related genes through RNA-binding protein CELF2 to induce zebrafish neurotoxicity
- Authors
- Wang, D., Wang, X., Huang, H., Wang, H.
- ID
- ZDB-PUB-210224-8
- Date
- 2021
- Source
- Journal of hazardous materials 413: 125414 (Journal)
- Registered Authors
- Keywords
- Alternative splicing, CELF2, Neurotoxicity, Triclosan, Zebrafish
- MeSH Terms
-
- Alternative Splicing
- Animals
- Brain
- RNA-Binding Proteins
- Triclosan*/toxicity
- Zebrafish/genetics
- PubMed
- 33621777 Full text @ J. Hazard. Mater.
Citation
Wang, D., Wang, X., Huang, H., Wang, H. (2021) Triclosan regulates alternative splicing events of nerve-related genes through RNA-binding protein CELF2 to induce zebrafish neurotoxicity. Journal of hazardous materials. 413:125414.
Abstract
Herein, we demonstrated that triclosan (TCS) induced neurotoxicity mediated by pre-mRNA alternative splicing (AS). TCS exposure resulted in a series of phenotypic malformations, abnormal locomotor behavior, circadian rhythm disorder and inhibited AChE activity. High throughput mRNA sequencing revealed that TCS regulated the AS events of nerve-related genes. Meanwhile, abnormal expression was observed in marker genes related to nerve cell migration, axon guidance and myelination. The expression of mitochondrial apoptosis activator bcl2l11 was significantly increased under TCS exposure. Interestingly, CELF2 as one of the important RNA-binding proteins was closely related to the AS events, and its mRNA and protein expression levels were significantly increased in zebrafish brain under acute or chronic TCS exposure. Functional knock-down and over-expression of celf2 confirmed that TCS led to nervous system injury and developmental defects through the CELF2-mediated AS events of genes (mbpa, mef2d, u2af2b and matn3b). Histopathological injury, phenotypic malformation, abnormal locomotor behavior and changes in neuromarkers all confirmed the biological functions of CELF2 in zebrafish brain. These findings demonstrate that TCS might regulate some of the AS events of nerve-related genes through upregulating the expression of CELF2. Thus, CELF2 may serve as a target for the prevention, diagnosis and treatment of contaminant-induced neurological diseases.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping