RNA化学蛋白质学 揭示了N6甲基氨酸 (m6A) 调节的蛋白质-RNA相互作用体
A Emilia Arguello1, Amanda N DeLiberto1, Ralph E Kleiner1
1Department of Chemistry, Princeton University , Princeton, New Jersey 08544, United States.
Journal of the American Chemical Society
|November 16, 2017
概括
这项研究揭示了N6-甲基氨酸 (m6A) 修改如何影响蛋白质相互作用. 研究人员发现了结合m6A的新蛋白质,并发现它破坏了压力颗粒蛋白的结合.
科学领域:
- 生物化学
- 分子生物学
- 蛋白质组学
背景情况:
- 经转录RNA的修改调节了mRNA的功能.
- 对于RNA修饰效应的生物化学机制的了解很少.
- N6 - 甲基氨酸 (m6A) 是真核生物中最丰富的内部RNA修饰物.
研究的目的:
- 开发一种化学蛋白质学方法来描述由m6A调节的RNA-蛋白相互作用.
- 识别与m6A修饰RNA相互作用的蛋白质.
- 阐明m6A函数的生化机制.
主要方法:
- 开发一种化学蛋白质组学策略.
- 使用含有合成氨酸的RNA探针进行光交叉链接.
- 定量蛋白质组学来分析RNA与蛋白质的相互作用.
主要成果:
- 已识别出已知的6个A相互作用体 (YTH域蛋白,ALKBH5).
- 发现了新的m6A读者:FMR1和LRPPRC,与人类疾病相关的蛋白质.
- 发现m6A通过压力颗粒蛋白 (G3BP1/2,USP10,CAPRIN1,RBM42) 破坏了RNA结合.
结论:
- 这项研究提出了检测RNA修饰相互作用的一般策略.
- 揭示了M6A功能背后的新生化学机制.
- 突出了m6A在调节压力颗粒动态和与疾病相关的蛋白相互作用中的作用.
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