通过监测子最佳性来结合mRNA衰变和翻译的DEAD-Box蛋白 Dhh1p
Aditya Radhakrishnan1, Ying-Hsin Chen2, Sophie Martin2
1Program in Molecular Biophysics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
Cell
|September 20, 2016
概括
死亡盒蛋白 Dhh1p 作为核糖体速度的传感器,专门针对具有非最佳代码的mRNA. 这种机制将转化延长率与mRNA衰变途径联系在一起.
科学领域:
- 分子生物学
- 遗传学
- 生物化学
背景情况:
- 转化延长的速度显著影响mRNA的半衰期,这取决于代码体.
- 转化延长和mRNA衰变之间的精确通信机制在很大程度上是未知的.
研究的目的:
- 研究DEAD-box蛋白Dh1p在感知子最佳性的作用及其对mRNA衰变的影响.
- 阐明核糖体速度如何影响mRNA降解途径.
主要方法:
- 分析mRNA降解率与代码子最佳性和Dh1p存在的关系.
- 进行生物化学实验以评估 Dhh1p 与 mRNA 的相关性.
- 使用Dh1p过度表达的mRNA研究核糖体积累.
- 检查Dh1p与核糖体之间的体内物理相互作用.
主要成果:
- 由于非最佳的编码子导致的翻译延长较慢的mRNA以Dh1p依赖的方式被特别降解.
- Dhh1p优先结合具有次优代码选择的mRNA.
- 这些mRNA的降解对缓慢移动的核糖体数量敏感.
- Dhh1p过度表达导致低编码优度mRNA和编码的核糖体积聚.
- 在体内,DH1p与核糖体进行物理相互作用.
结论:
- Dhh1p作为核糖体速度的传感器,将翻译效率与mRNA命运联系起来.
- 这种机制的目标是抑制和随后的衰变.
- 这些发现揭示了连接转化控制和mRNA稳定的新途径.
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