在RNA中N6-甲基亚丁素的结构和热力学:一个弹加载的基调修改
Caroline Roost1, Stephen R Lynch, Pedro J Batista
1Department of Chemistry, ‡Howard Hughes Medical Institute and Program in Epithelial Biology, Stanford University , Stanford, California 94305, United States.
Journal of the American Chemical Society
|January 23, 2015
概括
甲基氨酸 (m(6) A) 改变RNA结构,破坏双链区域的稳定,但稳定单链区域. 这种修改会影响RNA的二次结构和细胞过程.
科学领域:
- 分子生物学分子生物学
- 生物化学 生物化学
- 在RNA生物学,RNA生物学.
背景情况:
- 甲基氨酸 (m(6) 是一种普遍存在的RNA修饰.
- m(6) A与RNA降解,局部化和拼接有关.
- 对于m(6) A的功能,其精确的分子机制尚不清楚.
研究的目的:
- 阐明m(6) A修改对RNA的结构和热力学影响.
- 研究m(6)A如何在细胞环境中影响RNA二级结构.
主要方法:
- 2D核磁共振光谱测定具有或没有m的RNA双重结构.
- 在RNA复杂体中测量了m(6) A的热力学测量.
- 转录组全方位核酶映射以分析人体细胞中甲基化RNA二次结构.
主要成果:
- m(6) A诱导甲基氨基基组的构造变化,从syn转变为anti,将甲基组定位在主要槽中.
- m(6) A会使RNA复杂体不稳定到0.5-1.7 kcal/mol.
- m(6) 在单链区域中,A显著稳定未配对RNA基.
- 甲基化腺素显示出与修饰相邻的单链结构的倾向.
结论:
- m(6) A对RNA结构表现出上下文依赖的影响,破坏双重复合的稳定,同时稳定单链区域.
- 这些由m(6)A调解的结构变化可能有助于其在RNA代谢中的调节作用.
- 这些发现提供了关于m(6)A如何在结构层面上影响RNA功能的机制性见解.
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