结合部位m6甲基化阻止U2AF35的结合以抑制RNA结合
Mateusz Mendel1, Kamila Delaney1, Radha Raman Pandey1
1Department of Molecular Biology, Science III, University of Geneva, 30 Quai Ernest-Ansermet, 1211 Geneva 4, Switzerland.
Cell
|April 30, 2021
概括
通过METT-10进行的N6-甲基氨酸 (m6A) RNA修饰抑制了C. elegans中的S-腺甲氨酸合成酶前mRNA拼接. 这种由饮食触发的m6A开关调节了SAM稳态,并且在哺乳动物中保持了拼接抑制.
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:
- N6-甲基氨酸 (m6A) 是一种影响mRNA命运的流行RNA修饰.
- 在C. elegans中,m6A编写器METT-10是小鼠METTL16的正统产物.
研究的目的:
- 研究METT-10在调节S-adenosylmethionine (SAM) 合成酶前mRNA剪接中的作用.
- 阐明m6A介导的拼接抑制及其保存机制.
主要方法:
- RNA测序和分析
- 拼接试验
- 蛋白质生产分析
- 研究蛋白质-RNA相互作用的生物化学测试
主要成果:
- 在C. elegans中,METT-10将m6A沉积在SAM合成酶前mRNA的3'拼接部位上.
- 这种m6A修饰抑制了拼接和蛋白质的产生,作为一种适应饮食的开关.
- 在哺乳动物中,通过3' 拼接位m6A保持拼接抑制,防止U2AF35结合.
结论:
- 在3'拼接部位的m6A修饰是调节拼接的古老机制.
- 这种途径控制SAM合成酶的表达和适应饮食的平衡.
- 这些发现揭示了RNA介导的拼接控制的保存机制,对基因调节有影响.
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