动态m(6) mRNA甲基化指导热冲击反应的转化控制
Jun Zhou1, Ji Wan1, Xiangwei Gao1
1Division of Nutritional Sciences, Cornell University, Ithaca, New York 14853, USA.
Nature
|October 13, 2015
概括
热冲击应激会在mRNA5'未翻译区域 (5'UTR) 中触发N(6) - 甲基氨酸 (m(6) A) 修饰. 这种动态甲基化促进了独立于的转化,增强了应激反应.
科学领域:
- 分子生物学
- 核糖核酸生物学
- 基因表达的调节
背景情况:
- 甲基氨酸 (m(6) 是一种具有多种作用的流行mRNA修饰.
- 在哺乳动物mRNA中分布不对称,在5'未翻译区域 (5'UTR) 的甲基化较少.
- 对于5'UTR m(6) A的调节和功能,特别是在翻译启动方面,人们对其了解甚少.
研究的目的:
- 在压力条件下研究5'UTR m(6) A的调节和功能.
- 确定m(6) A在热冲击期间的mRNA翻译启动中的作用.
- 阐明在压力下选择性mRNA翻译的机制.
主要方法:
- 对热冲击反应的mRNA甲基化模式的分析.
- 研究m(6) A结合蛋白 (YTHDF2) 和甲基酶 (FTO) 的局部化和功能.
- 使用报告测定和特定mRNA实例 (Hsp70) 评估5'UTR m(6) A对翻译启动的影响.
主要成果:
- 在新转录的mRNA的5'UTR中诱导偏好的m(6) A甲基化.
- 压力诱导的YTHDF2的核定位通过抑制FTO脱甲基化来保持5'UTR甲基化.
- 增加的5'UTR m(6) A促进了独立于的翻译启动,以Hsp70 mRNA为例.
结论:
- 5'UTR m(6) A的动态调节对于细胞应激反应至关重要.
- 在5'UTR中的A提供了在热冲击下独立于盖的转换启动机制.
- 这项研究揭示了由m(6) A调解的热冲击反应中的新型转化控制途径.
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