文献类型： 外文期刊

作者： Lin, Jiebo ¹ ; Zhan, Guankai ¹ ; Liu, Jinfeng ¹ ; Maimaitiyiming, Yasen ¹ ; Deng, Zhiping ⁷ ; Li, Baohua ⁸ ; Su, Kunhui ¹ ; Chen, Jiafeng ¹ ; Sun, Siqi ¹ ; Zheng, Wanlin ⁹ ; Yu, Xianghui ⁹ ; He, Feng ³ ; Cheng, Xiaodong ¹² ; Wang, Lingfang ¹ ; Shen, Bin ¹³ ; Yao, Ziqin ⁴ ; Yang, Xinquan ⁴ ; Zhang, Jian ¹ ; He, Wentao ¹ ; Wu, Hengyu ¹ ; Naranmandura, Hua ⁵ ; Chang, Kao-Jung ¹⁵ ; Min, Junxia ¹⁶ ; Ma, Jun ³ ; Bjoerklund, Mikael ¹⁷ ; Xu, Peng-Fei ³ ; Wang, Fudi ⁴ ; Hsu, Chih-Hung ¹ ;

作者机构： 1.Zhejiang Univ, Womens Hosp, Affiliated Hosp 4, Sch Med, Hangzhou 310006, Peoples R China

2.Zhejiang Univ, Sch Med, Dept Environm Med, Hangzhou 310006, Peoples R China

3.Zhejiang Univ, Inst Genet, Int Sch Med, Yiwu 322000, Peoples R China

4.Zhejiang Univ, Affiliated Hosp 2, Sch Publ Hlth, State Key Lab Expt Hematol,Sch Med, Hangzhou 310058, Peoples R China

5.Zhejiang Univ, Affiliated Hosp 1, Sch Med, Dept Hematol, Hangzhou 310000, Peoples R China

6.Zhejiang Univ, Sch Med, Dept Publ Hlth, Hangzhou 310000, Peoples R China

7.Zhejiang Acad Agr Sci, Inst Virol & Biotechnol, State Key Lab Managing Biot & Chem Threats Qual &, Hangzhou 310000, Peoples R China

8.Zhejiang Univ, Womens Hosp, Sch Med, Dept Obstet, Hangzhou 310000, Peoples R China

9.Zhejiang Univ, Sch Med, Womens Hosp, Hangzhou 310000, Peoples R China

10.Zhejiang Univ, Inst Genet, Sch Med, Hangzhou 310000, Peoples R China

11.Zhejiang Prov Key Lab Genet & Dev Disorders, Hangzhou 310058, Peoples R China

12.Zhejiang Univ, Womens Hosp, Sch Med, Zhejiang Prov Key Lab Precis Diag & Therapy Major, Hangzhou 310000, Peoples R China

13.Nanjing Med Univ, Womens Hosp, Nanjing Matern & Child Hlth Care Hosp, Ctr Global Hlth,State Key Lab Reprod Med,Gusu Sch, Nanjing 211166, Peoples R China

14.Univ South China, Affiliated Hosp 1, Sch Publ Hlth, Sch Pharmaceut Sci,Basic Med Sci,Hengyang Med Sch, Hengyang 421001, Peoples R China

15.Taipei Vet Gen Hosp, Dept Med Res, Taipei 11217, Taiwan

16.Zhejiang Univ, Sch Med, Inst Translat Med, Affiliated Hosp 1,Canc Ctr, Hangzhou 310058, Peoples R China

17.Zhejiang Univ Univ Edinburgh ZJU UoE Inst, Haining 314400, Peoples R China

18.Univ Edinburgh, Med Sch, Coll Med & Vet Med, Biomed Sci, Edinburgh EH8 9JZ, Scotland

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.