ALKBH5 的失序的 C 终端促进了相位分离,并促进了光斑组合
Xiaoyang Qin1, Yan Long1, Xue Bai2
1State Key Laboratory of Experimental Hematology, The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Key Laboratory of Medical Epigenetics, Department of Cell Biology, Tianjin Medical University, Tianjin, China.
The Journal of biological chemistry
|July 20, 2023
概括
RNA脱甲基酶ALKBH5通过相位分离驱动斑形成,稳定NEAT1并促进癌细胞在缺氧下入侵.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 抛光镜 (PS) 是由NEAT1 lncRNA和NONO和SFPQ等蛋白质调节的核体.
- 以前已经证明ALKBH5,一种m6A脱甲基酶,可以稳定NEAT1并在缺氧下促进PS组装.
- 这些事件的时空协调仍然不清楚.
研究的目的:
- 阐明协调ALKBH5活动,NEAT1稳定和在缺氧下PS组装的机制.
- 研究ALKBH5相分离在PS形成和缺氧诱导的细胞反应中的作用.
主要方法:
- 同免疫沉以评估PS.内的ALKBH5蛋白相互作用.
- 光显微镜观察ALKBH5相位分离和PS形成动态.
- 在野生型和突变ALKBH5细胞中分析NEAT1 m6A标记和稳定性.
- 低氧诱导的癌细胞入侵的评估.
主要成果:
- ALKBH5直接与PS蛋白结合,并通过其C端内在无序区域 (cIDR) 形成相隔滴.
- 缺氧会在PS中触发ALKBH5的快速凝结,导致NEAT1脱甲基化和稳定,然后ALKBH5的表达会增加.
- 缺少cIDR的ALKBH5会影响缺氧诱导的PS形成,NEAT1脱甲基化和NEAT1不稳定.
- ALKBH5-cIDR对于缺氧驱动的癌细胞入侵至关重要.
结论:
- ALKBH5利用相位分离来形成PS组件的正反循环,将其纳入PS与NEAT1稳定联系起来.
- ALKBH5介导的相分离是一种关键的分子机制,协调细胞对缺氧的反应,包括癌症的进展.
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