The DExD/H box ATPase Dhh1 functions in translational repression, mRNA decay, and processing body dynamics

The DExD/H box ATPase Dhh1 functions in translational repression, mRNA decay, and processing body dynamics
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DOI:
10.1083/jcb.201007151
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发表时间:
2011-08-22
影响因子:
7.8
通讯作者:
Weis, Karsten
Weis, Karsten
中科院分区:
生物学1区
文献类型:
--
作者:
Carroll, Johanna S.;Munchel, Sarah E.;Weis, Karsten

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信使核糖核酸(mrna)的翻译、储存和降解是基因表达转录后控制的关键步骤,但mrna如何在这些过程之间转运仍然知之甚少。在本文中,我们对DExD/ H盒腺苷三磷酸酶(ATPase) Dhh1进行了功能表征,该酶是mrna细胞质命运的关键调节因子。通过在酵母中进行mRNA捆绑实验,我们发现Dhh1足以将mRNA从活性状态转移到翻译抑制状态。在积极分裂的细胞中,翻译抑制之后是mRNA衰变;然而,删除5‘-3’衰变路径的组件将这些过程解耦。然而,当Dhh1的ATP酶活性直接与mRNA连接时,不需要诱导翻译抑制和mRNA衰变,ATP水解调节加工体动力学和Dhh1从这些rna -蛋白颗粒中释放。我们的研究结果将Dhh1置于翻译和衰变的界面,控制mRNA是否被翻译、存储或衰变。
Translation, storage, and degradation of messenger ribonucleic acids (mRNAs) are key steps in the post-transcriptional control of gene expression, but how mRNAs transit between these processes remains poorly understood. In this paper, we functionally characterized the DExD/ H box adenosine triphosphatase (ATPase) Dhh1, a critical regulator of the cytoplasmic fate of mRNAs. Using mRNA tethering experiments in yeast, we showed that Dhh1 was sufficient to move an mRNA from an active state to translational repression. In actively dividing cells, translational repression was followed by mRNA decay; however, deleting components of the 5'-3' decay pathway uncoupled these processes. Whereas Dhh1's ATPase activity was not required to induce translational inhibition and mRNA decay when directly tethered to an mRNA, ATP hydrolysis regulated processing body dynamics and the release of Dhh1 from these RNA-protein granules. Our results place Dhh1 at the interface of translation and decay controlling whether an mRNA is translated, stored, or decayed.