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YTHDF2-mediated regulations bifurcate BHPF-induced programmed cell deaths.
- Source :
-
National science review [Natl Sci Rev] 2023 Aug 28; Vol. 10 (12), pp. nwad227. Date of Electronic Publication: 2023 Aug 28 (Print Publication: 2023). - Publication Year :
- 2023
-
Abstract
- N <superscript>6</superscript> -methyladenosine (m <superscript>6</superscript> A) is a critical regulator in the fate of RNA, but whether and how m <superscript>6</superscript> A executes its functions in different tissues remains largely obscure. Here we report downregulation of a crucial m <superscript>6</superscript> 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 <superscript>6</superscript> A- gch1 for cardiomyocyte ferroptosis, and decreased YTHDF2-mediated m <superscript>6</superscript> A- sting1 decay for caudal vein plexus (CVP) apoptosis. The two distinct YTHDF2-mediated m <superscript>6</superscript> 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.<br /> (© The Author(s) 2023. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)
Details
- Language :
- English
- ISSN :
- 2053-714X
- Volume :
- 10
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- National science review
- Publication Type :
- Academic Journal
- Accession number :
- 38152479
- Full Text :
- https://doi.org/10.1093/nsr/nwad227