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依赖N(6) -甲基氨酸的RNA结构开关调节RNA-蛋白相互作用
Nian Liu1, Qing Dai1, Guanqun Zheng2
1Department of Chemistry, The University of Chicago, Chicago, Illinois 60637, USA.
Nature
|February 27, 2015
概括
这种N(6) - 甲基氨酸 (m(6) A) 修饰作为一个"m(6) A开关",改变RNA结构以控制RNA-蛋白相互作用. 这种机制通过影响RNA结合蛋白进入RNA结合基因的模式来调节基因表达和RNA成熟.
科学领域:
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 在RNA生物学,RNA生物学.
背景情况:
- RNA结合蛋白 (RBPs) 通过与RNA结合基因 (RBMs) 相互作用来调节细胞过程.
- 局部RNA结构可能会阻碍RBM的可访问性,限制RBP相互作用.
- N(6) - 甲基氨酸 (m(6) A) 是一种关键的mRNA修饰,影响RNA命运,但其在调节RBP进入结构化的RBM中的作用尚不清楚.
研究的目的:
- 调查m(6)A在控制RNA结构依赖RBMs对RNA蛋白相互作用的可访问性方面的作用.
- 阐明m(6)A影响RBP结合和随后的基因调节的机制.
- 识别和描述RBP结合位点的A介导调节.
主要方法:
- 在人体细胞中利用可光激活的核核糖增强交联和免疫沉降 (PAR-CLIP) 和抗m(6) A免疫沉降 (MeRIP).
- 结合PAR-CLIP和MeRIP来识别m(6) A-依赖的RBP结合位点,称为"m(6) A-开关".
- 评估了全球m(6)A减少对RBP结合和基因表达的影响.
主要成果:
- 确定了与异质核核核糖核蛋白C (HNRNPC) 结合部位相关的39,060m(6) A-交换机.
- 证明m(6) A改变局部RNA结构,促进HNRNPC与mRNA和lncRNA中的RBM结合.
- 观察到m(6)A减少减少了HNRNPC结合在2,798个高可信度m(6)A开关,影响了目标mRNA丰度和替代拼接.
结论:
- m(6) A作为一个"m(6) A开关",调节RNA结构以调节RBP的可访问性和功能.
- 这种机制通过控制RBP与RBM结合,影响基因表达和RNA成熟.
- 为理解RNA修饰编码的细胞生物学和RNA-蛋白相互作用提供了一个新的框架.
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