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- Title
YTHDF2-mediated regulations bifurcate BHPF-induced programmed cell deaths.
- Authors
Lin, Jiebo; Zhan, Guankai; Liu, Jinfeng; Maimaitiyiming, Yasen; Deng, Zhiping; Li, Baohua; Su, Kunhui; Chen, Jiafeng; Sun, Siqi; Zheng, Wanlin; Yu, Xianghui; He, Feng; Cheng, Xiaodong; Wang, Lingfang; Shen, Bin; Yao, Ziqin; Yang, Xinquan; Zhang, Jian; He, Wentao; Wu, Hengyu
- 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.
- Subjects
APOPTOSIS; CELL death; PLASTIC products manufacturing
- Publication
National Science Review, 2023, Vol 10, Issue 12, p1
- ISSN
2095-5138
- Publication type
Article
- DOI
10.1093/nsr/nwad227