N6-甲基氨酸标记了初级微RNA用于加工
Claudio R Alarcón1, Hyeseung Lee1, Hani Goodarzi1
1Laboratory of Systems Cancer Biology, Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.
Nature
|March 25, 2015
概括
甲基转移酶类3 (METTL3) 将m(6) A标记添加到primiRNA中,使得DGCR8识别和microRNA处理成为可能. 这种修改对于miRNA生物发生和全球miRNA水平至关重要.
科学领域:
- 分子生物学分子生物学
- 在RNA生物学,RNA生物学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 微RNA (miRNA) 生物发生始于微处理器复合体 (DGCR8/DROSHA) 的初级miRNA (pri-miRNA) 处理.
- 对于DGCR8对其他RNA结构上的primiRNAs识别的确切机制尚不清楚.
研究的目的:
- 阐明DGCR8识别和结合primiRNAs的机制.
- 确定调节miRNA生物发生的初始步骤的因素.
主要方法:
- 细胞实验涉及METTL3耗尽和功能的增加.
- 生物化学测定包括体外加工反应.
- 对primiRNA和成熟miRNA水平的分析.
主要成果:
- 在N(6) - 甲基亚丁素 (m(6) A部位上甲基化METTL3的pri-miRNAs,标记它们为DGCR8结合.
- METTL3的枯竭减少了DGCR8-pri-miRNA的相互作用,导致成熟miRNA的减少和primiRNA水平的增加.
- 在体外研究证实了m(6)A足够用于primiRNA处理;METTL3在全球范围内增强了miRNA成熟.
结论:
- 由METTL3介导的m(6)A修饰是一种关键的转录后调节器,促进了DGCR8的primi-miRNA识别和处理.
- 这一发现揭示了一种控制miRNA生物发生的新机制.
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