通过促进YTHDF2介导的PIK3R2mRNA降解,YTHDF2相分离促进了酸盐诱导的氧化应激
Jin Man1, Qian Zhang1, Tianhe Zhao1
1Department of Environmental and Occupational Health, West China School of Public Health, Sichuan University, Chengdu, Sichuan 610041, China.
International journal of biological macromolecules
|June 5, 2025
概括
暴露会增加YTHDF2蛋白质,促进氧化应激. YTHDF2相位分离降解PIK3R2mRNA,抑制一个关键途径并恶化毒性.
科学领域:
- 毒理学 毒理学 毒理学
- 分子生物学分子生物学
- 环境健康 环境健康
背景情况:
- 氧化应激是毒性的主要机制.
- 在引起的氧化应激中,YTH N6-甲基氨酸RNA结合蛋白2 (YTHDF2) 液-液相分离 (LLPS) 的作用尚不清楚.
- 了解YTHDF2在毒性中的作用至关重要.
研究的目的:
- 研究YTHDF2在引起的氧化应激中的作用.
- 为了阐明YTHDF2相分离在对的反应中的机制.
- 为了确定YTHDF2介导的毒性所涉及的特定相互作用.
主要方法:
- 在暴露下,人类角质细胞 (HaCaT细胞) 中评估了YTHDF2水平.
- 利用YTHDF2的敲击来评估其对引起的氧化应激的影响.
- 研究了YTHDF2与m6A修饰的PIK3R2mRNA的结合及其在相分离中的作用.
主要成果:
- 在引起的氧化应激过程中,YTHDF2水平增加.
- 敲除YTHDF2显著降低了引起的氧化应激.
- 由m6A驱动的YTHDF2相分离导致PIK3R2mRNA降解.
- 这种降解抑制了PI3K-AKT信号通路,导致氧化应激.
结论:
- YTHDF2的液-液相分离 (LLPS) 加剧了引起的氧化应激.
- 通过降解m6A修饰的PIK3R2mRNA,YTHDF2促进了的毒性.
- 这项研究为毒性分子机制提供了新的见解.
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