YTHDF2-mediated regulations bifurcate BHPF-induced programmed cell deaths

文献类型： 外文期刊

第一作者： Lin, Jiebo

作者： Lin, Jiebo;Zhan, Guankai;Liu, Jinfeng;Maimaitiyiming, Yasen;Su, Kunhui;Chen, Jiafeng;Sun, Siqi;Wang, Lingfang;Zhang, Jian;He, Wentao;Wu, Hengyu;Hsu, Chih-Hung;Lin, Jiebo;Zhan, Guankai;Liu, Jinfeng;Maimaitiyiming, Yasen;Su, Kunhui;Chen, Jiafeng;Sun, Siqi;Wang, Lingfang;Zhang, Jian;He, Wentao;Wu, Hengyu;Hsu, Chih-Hung;Lin, Jiebo;Zhan, Guankai;Liu, Jinfeng;Maimaitiyiming, Yasen;Su, Kunhui;Chen, Jiafeng;Sun, Siqi;He, Feng;Wang, Lingfang;Zhang, Jian;He, Wentao;Wu, Hengyu;Ma, Jun;Xu, Peng-Fei;Hsu, Chih-Hung;Liu, Jinfeng;Yao, Ziqin;Yang, Xinquan;Wang, Fudi;Maimaitiyiming, Yasen;Naranmandura, Hua;Maimaitiyiming, Yasen;Naranmandura, Hua;Deng, Zhiping;Li, Baohua;Zheng, Wanlin;Yu, Xianghui;He, Feng;Ma, Jun;Xu, Peng-Fei;Zheng, Wanlin;Yu, Xianghui;He, Feng;Ma, Jun;Xu, Peng-Fei;Zheng, Wanlin;Yu, Xianghui;He, Feng;Ma, Jun;Cheng, Xiaodong;Wang, Lingfang;Shen, Bin;Yao, Ziqin;Yang, Xinquan;Wang, Fudi;Chang, Kao-Jung;Min, Junxia;Bjoerklund, Mikael;Bjoerklund, Mikael

作者机构：

关键词： RNA m(6)A modification; programmed cell deaths; bifurcation role of YTHDF2; environmental stress and m(6)A regulation; fluorene-9-bisphenol (BHPF)

期刊名称：NATIONAL SCIENCE REVIEW （ 影响因子：20.6； 五年影响因子：22.3 ）

ISSN： 2095-5138

年卷期： 2023 年 10 卷 12 期

页码：

收录情况： SCI

摘要： N-6-methyladenosine (m(6)A) is a critical regulator in the fate of RNA, but whether and how m(6)A executes its functions in different tissues remains largely obscure. Here we report downregulation of a crucial m(6)A 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 m(6)A-gch1 for cardiomyocyte ferroptosis, and decreased YTHDF2-mediated m(6)A-sting1 decay for caudal vein plexus (CVP) apoptosis. The two distinct YTHDF2-mediated m(6)A 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.

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