人体细胞中的5'终端尼古丁胺二核酸通过DXO介导的DNA分解促进RNA衰变
Xinfu Jiao1, Selom K Doamekpor2, Jeremy G Bird3
1Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854, USA.
Cell
|March 12, 2017
概括
哺乳动物细胞有一个新的RNA盖,尼古丁胺二核酸 (NAD+),与m7G盖不同,促进RNA衰变. DXO酶可以去除这些NAD+盖,调节细胞NAD+盖的RNA水平.
科学领域:
- 分子生物学
- 核糖核酸生物学
- 生物化学
背景情况:
- 单核mRNA通常具有N7-甲基关素 (m7G) 盖,这对翻译和稳定性至关重要.
- 哺乳动物细胞具有另一种5'端盖:尼古丁胺二核酸 (NAD+).
- 与m7G帽不同的是,NAD+帽阻碍翻译并促进mRNA衰变.
研究的目的:
- 建立NAD+作为一种替代性哺乳动物RNA帽.
- 确定负责去除NAD+盖的酶.
- 阐明NAD+除及其细胞调节的机制.
主要方法:
- 用3'-NADP+对DXO/Rai1酶进行联合结晶.
- 酶测试以研究脱NAD反应.
- 细胞实验涉及去除DXO以观察NAD+覆盖的RNA水平.
主要成果:
- DXO/Rai1酶有效地去除NAD+盖,产生NAD+和5'酸RNA.
- 结晶结构揭示了脱NADding反应的分子机制.
- 细胞中的DXO耗尽导致NAD+封顶mRNA和snoRNA的水平增加.
结论:
- NAD+被确定为一种新的哺乳动物RNA帽.
- DXO作为一个deNADding酶,调节细胞NAD+覆盖RNA水平.
- NAD+限制影响RNA衰变路径,并且可以发生在经过处理的RNA终端上.
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