UPF1 ATPase自抑制和激活调节RNA结合动力学和NMD效率
Joseph H Chapman1, Alice M Youle1, Acadia L Grimme1
1Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA.
bioRxiv : the preprint server for biology
|December 11, 2023
概括
这种RNA螺旋酶是UPF1
科学领域:
- 分子生物学分子生物学
- 生物化学 生物化学
- 遗传学 遗传学 是一个
背景情况:
- 无意中介的mRNA衰变 (NMD) 是一个关键的监测途径,可以消除异常的mRNA.
- RNA螺旋酶UPF1是NMD的核心因素,与mRNA和衰变机械相互作用.
- UPF1的酶活性由其与UPF2的相互作用来调节,在关闭 (抑制) 和开放 (活性) 状态之间进行过渡.
研究的目的:
- 研究UPF1激活状态的动力特性.
- 确定UPF1-核酸相互作用动力学对NMD效率的影响.
- 澄清NMD中UPF1,UPF2和RNA结合/解离之间的相互作用.
主要方法:
- 生物化学分析测量UPF1结合和解离动力学.
- 对UPF1-RNA相互作用的计算建模.
- 在NMD测定中分析了具有改变动力性质的UPF1突变.
主要成果:
- 激活的UPF1状态表现出较慢的核酸结合和更快的ATP刺激解离.
- UPF1-RNA相互作用在很大程度上发生在细胞中独立于UPF2结合.
- 变异的RNA解离动力学突变体显示NMD缺陷.
- 活动依赖UPF2的UPF1突变对NMD目标仍然具有功能.
结论:
- UPF1-mRNA相互作用的动力学,而不仅仅是酶激活,对于NMD效率至关重要.
- UPF1与mRNA的动态相互作用是其在细胞mRNA质量控制中的功能关键决定因素.
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