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
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
Figures
Figure Gallery (4 images)
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
rj6TgTransgenic Insertion
    y1TgTransgenic Insertion
      1 - 2 of 2
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      Human Disease / Model
      No data available
      Sequence Targeting Reagents
      Target Reagent Reagent Type
      gch1MO1-gch1MRPHLNO
      mettl3MO1-mettl3MRPHLNO
      tnfaMO1-tnfaMRPHLNO
      ythdf2CRISPR4-ythdf2CRISPR
      ythdf2MO1-ythdf2MRPHLNO
      1 - 5 of 5
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      Fish
      No data available
      Antibodies
      No data available
      Orthology
      No data available
      Engineered Foreign Genes
      Marker Marker Type Name
      EGFPEFGEGFP
      1 - 1 of 1
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      Mapping
      No data available
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      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.