在5'帽中可逆甲基化控制mRNA稳定性
Jan Mauer1, Xiaobing Luo2, Alexandre Blanjoie3
1Department of Pharmacology, Weill Cornell Medicine, Cornell University, New York, New York 10065, USA.
Nature
|December 22, 2016
概括
在mRNA的5'端的N6,2'- O- dimethyladenosine (m6Am) 修饰增强了转录稳定性. 脂肪质量和与肥胖相关的蛋白质 (FTO) 逆转了m6Am标记,影响了mRNA的命运.
科学领域:
- 分子生物学
- 表观遗传学
- 核糖核酸生物学
背景情况:
- 在mRNA中的内部基因经历了影响细胞命运的修改.
- N6,2"-O-二甲基氨酸 (m6Am) 是mRNA的5'端的一个普遍变异,与7-甲基氨酸盖相邻.
研究的目的:
- 研究N6,2"-O-dimethyladenosine (m6Am) 作为影响细胞mRNA命运的可逆修饰的作用.
- 确定m6Am对mRNA稳定性及其调节的影响.
主要方法:
- 对m6Am修饰的全转录组映射.
- 评估与m6Am状态相关的mRNA稳定性
- 研究m6Am与切割酶DCP2之间的相互作用.
- 在m6Am上分析脂肪质量和与肥胖相关的蛋白质 (FTO) 的脱甲基活性.
主要成果:
- 与其他核酸开始的转录物相比,m6Am启动的转录物具有显著的稳定性.
- m6Am转录的增强稳定性归因于对mRNA分解酶DCP2的耐药性.
- 脂肪质量和与肥胖相关的蛋白质 (FTO) 选择性地去甲基化m6Am,这一过程与其对N6-甲基氨酸 (m6A) 的作用不同.
- 通过FTO介导的m6Am去甲基化导致mRNA稳定性降低.
结论:
- 在5'顶部的m6Am甲基化状态是一种动态和可逆的表体转录变异.
- 通过影响切割过程,m6Am修饰直接决定了mRNA的稳定性.
- 通过m6Am的动态脱甲基化,FTO在调节mRNA稳定性方面发挥着至关重要的作用.
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