m6A增强了mRNA的相分离潜力
Ryan J Ries1, Sara Zaccara1, Pierre Klein1
1Department of Pharmacology, Weill-Cornell Medical College, Cornell University, New York, NY, USA.
Nature
|July 12, 2019
概括
在mRNA中的N6-甲基氨酸 (m6A) 修饰驱动YTHDF蛋白质的液相分离. 在mRNA上的多个m6A位点充当支架,通过分区特定调节影响mRNA的命运.
科学领域:
- 生物化学
- 分子生物学
- 细胞生物学
背景情况:
- N6-甲基氨酸 (m6A) 是最丰富的mRNA修饰,影响细胞过程.
- m6A影响mRNA命运和细胞上下文影响的确切机制尚不清楚.
研究的目的:
- 研究细胞质m6A结合蛋白 (YTHDF1-3) 在mRNA调节中的作用.
- 阐明m6A介导的mRNA命运决定的基础生物物理机制.
主要方法:
- 在体外和细胞内的液态相分离试验.
- 对YTHDF蛋白与m6A修饰的mRNA相互作用的分析.
- 在分相细胞区内对mRNA局部化的研究.
主要成果:
- YTHDF1,YTHDF2和YTHDF3蛋白质经历液体-液体相分离.
- 具有多个m6A位点的mRNA显著增强了相分离,它们充当了支架.
- mRNA-YTHDF复合体分成P体和压力颗粒等内源区,导致调节的mRNA稳定性和翻译.
结论:
- m6A位点的数量和分布调节了转录组的相分离.
- 液-液相分离原理控制了m6A修饰的mRNA的细胞特性.
- 通过m6A介导的相分离提供了分区特异的mRNA调节机制.
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