PUBLICATION
YTHDF2-mediated regulations bifurcate BHPF-induced programmed cell deaths
- Authors
- Lin, J., Zhan, G., Liu, J., Maimaitiyiming, Y., Deng, Z., Li, B., Su, K., Chen, J., Sun, S., Zheng, W., Yu, X., He, F., Cheng, X., Wang, L., Shen, B., Yao, Z., Yang, X., Zhang, J., He, W., Wu, H., Naranmandura, H., Chang, K.J., Min, J., Ma, J., Björklund, M., Xu, P.F., Wang, F., Hsu, C.H.
- ID
- ZDB-PUB-231228-6
- Date
- 2023
- Source
- National science review 10: nwad227nwad227 (Journal)
- Registered Authors
- Min, Junxia, Wang, Fudi
- Keywords
- RNA m6A modification, bifurcation role of YTHDF2, environmental stress and m6A regulation, fluorene-9-bisphenol (BHPF), programmed cell deaths
- MeSH Terms
- none
- PubMed
- 38152479 Full text @ Natl Sci Rev
Citation
Lin, J., Zhan, G., Liu, J., Maimaitiyiming, Y., Deng, Z., Li, B., Su, K., Chen, J., Sun, S., Zheng, W., Yu, X., He, F., Cheng, X., Wang, L., Shen, B., Yao, Z., Yang, X., Zhang, J., He, W., Wu, H., Naranmandura, H., Chang, K.J., Min, J., Ma, J., Björklund, M., Xu, P.F., Wang, F., Hsu, C.H. (2023) YTHDF2-mediated regulations bifurcate BHPF-induced programmed cell deaths. National science review. 10:nwad227nwad227.
Abstract
N6-methyladenosine (m6A) is a critical regulator in the fate of RNA, but whether and how m6A executes its functions in different tissues remains largely obscure. Here we report downregulation of a crucial m6A reader, YTHDF2, leading to tissue-specific programmed cell deaths (PCDs) upon fluorene-9-bisphenol (BHPF) exposure. Currently, Bisphenol A (BPA) substitutes are widely used in plastic manufacturing. Interrogating eight common BPA substitutes, we detected BHPF in 14% serum samples of pregnant participants. In a zebrafish model, BHPF caused tissue-specific PCDs triggering cardiac and vascular defects. Mechanistically, BHPF-mediated downregulation of YTHDF2 reduced YTHDF2-facilitated translation of m6A-gch1 for cardiomyocyte ferroptosis, and decreased YTHDF2-mediated m6A-sting1 decay for caudal vein plexus (CVP) apoptosis. The two distinct YTHDF2-mediated m6A regulations and context-dependent co-expression patterns of gch1/ythdf2 and tnfrsf1a/ythdf2 contributed to YTHDF2-mediated tissue-specific PCDs, uncovering a new layer of PCD regulation. Since BHPF/YTHDF2-medaited PCD defects were also observed in mammals, BHPF exposure represents a potential health threat.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping