螺旋酶Ded1p控制了5' UTR中近同类转化启动码子的使用
Ulf-Peter Guenther1, David E Weinberg2,3,4, Meghan M Zubradt2,5
1Center for RNA Science and Therapeutics, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
Nature
|June 29, 2018
概括
死亡盒RNA酶Ded1p (及其哺乳动物正体DDX3) 通过控制近同源起始码子的使用来调节翻译启动,特别是在响应mRNA结构时. 这种机制对于蛋白质合成和半球变化等细胞过程至关重要.
科学领域:
- 分子生物学
- 遗传学
- 生物化学
背景情况:
- 在转化启动过程中,DEAD盒RNA酶Ded1p (酵母) 和DDX3 (哺乳动物) 是必不可少的.
- DDX3的失调与癌症和智力障碍有关,并且DDX3是病毒感染的目标.
- 在翻译启动过程中,Ded1p/ DDX3与RNA相互作用的确切机制尚不清楚.
研究的目的:
- 阐明Ded1p在翻译启动过程中的RNA参与中的作用.
- 为了研究Ded1p活动,mRNA结构和替代翻译开始密码体之间的联系.
- 了解这种调节程序在半球变化等过程中的生理相关性.
主要方法:
- 翻译,RNA结构和Ded1p-RNA结合的整体转录组分析.
- 评估了抑制Ded1p活动对5' 未翻译区域 (UTR) RNA结构和翻译启动的影响.
- 检查了Ded1p水平和变化过程中的替代翻译启动.
主要成果:
- Ded1p与mRNA进入通道的翻译前启动复合物相关.
- 抑制Ded1p活动导致5' UTR中的RNA结构增加,从而促进从上游近同源起始编码子的翻译启动.
- 抑制Ded1p导致主要开放的读取框架中的蛋白质合成减少,并激活变过程中的替代翻译启动位.
结论:
- 在5' UTR中,Ded1p通过控制位于mRNA结构附近的近同源启动码的选择来调节翻译启动.
- 一个连接Ded1p的调节程序,近同源启动密码子激活,和mRNA结构控制蛋白质合成.
- 这种Ded1p介导的调节在细胞过程中起着重要作用,包括半球变化.
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