通过YTHDF2介导的法规分化了由BHPF引起的编程细胞死亡.
Jiebo Lin1,2, Guankai Zhan1,2, Jinfeng Liu1,2,3
1Women's Hospital, The Fourth Affiliated Hospital, and Department of Environmental Medicine, Zhejiang University School of Medicine, Hangzhou 310006.
-9-双 (BHPF) 暴露会降低RNA调节器YTHDF2的调节,导致组织特异性的细胞死亡. 这一发现揭示了编程细胞死亡 (PCD) 的新机制,并强调了BHPF作为潜在的健康风险.
科学领域:
- 表观遗传学和RNA生物学
- 毒理学和环境健康
- 发育生物学是发展生物学.
背景情况:
- N6-甲基氨酸 (m6A) 是一种关键的RNA调节剂,但其组织特异性功能尚未完全理解.
- 双A (BPA) 替代物如-9-双 (BHPF) 是常见的,并且在孕妇中检测到BHPF.
- 组织特异性编程细胞死亡 (PCD) 机制需要进一步阐明.
研究的目的:
- 研究m6A阅读器YTHDF2在由BHPF诱导的组织特异性PCD中的作用.
- 探索BHPF介导毒性的基础分子机制.
- 评估BHPF暴露的潜在健康风险.
主要方法:
- 在人血清样本中研究了八种常见的BPA替代品来检测BHPF.
- 利用斑马鱼模型研究由BHPF诱导的组织特异性PCD.
- 分析了BHPF对YTHDF2表达及其下游目标 (m6A-gch1和m6A-sting1) 的影响.
- 检查了与YTHDF2和PCD相关的基因共同表达模式.
主要成果:
- 在14%的怀孕参与者血清样本中检测到BHPF.
- 在斑马鱼中,BHPF暴露引起了组织特异性PCD,导致心脏,血管和尾脉缺陷.
- BHPF降低了YTHDF2的调节,通过gch1翻译影响心肌细胞铁亡,通过sting1衰变影响尾静脉囊亡.
- 独特的YTHDF2介导的m6A规则和共同表达模式有助于组织特异性PCD.
结论:
- 通过降低m6A阅读器YTHDF2.2.的调节,BHPF暴露会诱导组织特异性PCD.
- 这项研究揭示了一种新的PCD调节层,涉及YTHDF2介导的m6A修饰.
- BHPF对健康构成潜在威胁,特别是对孕妇和正在发育的生物体,这是哺乳动物中保存的机制所证明的.
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