Dbp5, Gle1-IP6 and Nup159 A working model for mRNP export
Dbp5, Gle1-IP6 and Nup159 A working model for mRNP export
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DOI：
10.4161/nucl.2.6.17881
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发表时间：
2011-11-01
期刊：
影响因子：
3.7
通讯作者：
Wente, Susan R.
中科院分区：
文献类型：
--
作者：
Folkmann, Andrew W.;Noble, Kristen N.;Wente, Susan R.
基因表达是一个逐步过程，涉及不同的细胞过程，包括转录、mRNA (mRNA) 加工、mRNA 输出和翻译。当 mRNA 合成时，蛋白质与 RNA 结合形成信使核糖核蛋白颗粒 (mRNP)。先前的研究表明，这些 mRNP 的 RNA 结合蛋白组成是动态的，随着 mRNP 在基因表达的不同步骤中移动而变化，并在这些事件中发挥关键作用。这一成熟过程中的一个重要步骤发生在核孔复合体 (NPC) 的细胞质表面，其中与肌醇六磷酸 (IP6) 结合的输出蛋白 Gle1 在空间上激活 DEAD-box 蛋白 Dbp5 的 ATP 水解和 mRNA 重塑活性。我们实验室和其他实验室最近的工作为 Dbp5 的功能和调控提供了重要的见解。其中包括对 Dbp5 RNP 重塑机制的更详细解释、Gle1-IP6 在刺激 Dbp5 ATPase 活性中的作用，以及 Nup159 调节 Dbp5 的新范例的识别。基于体外生化测定、X射线晶体学和相应的体内表型，我们在此提出了mRNP通过NPC输出期间的Dbp5循环的更新模型。这考虑了所有可用的数据，并为未来的研究提供了平台。
Gene expression is a stepwise process involving distinct cellular processes including transcription, mRNA (mRNA) processing, mRNA export, and translation. As mRNAs are being synthesized, proteins associate with the RNA to form messenger ribonucleoprotein particles (mRNPs). Previous studies have demonstrated that the RNA-binding protein composition of these mRNPs is dynamic, changing as the mRNP moves through the different steps of gene expression, and playing a critical role in these events. An important step during this maturation process occurs at the cytoplasmic face of the nuclear pore complex (NPC) where the export protein Gle1 bound to inositol hexakisphosphate (IP6) spatially activates the ATP-hydrolysis and mRNP-remodeling activity of the DEAD-box protein Dbp5. Recent work from our laboratory and others has provided important insights into the function and regulation of Dbp5. These include a more detailed explanation of the mechanism of Dbp5 RNP remodeling, the role of Gle1-IP6 in stimulating Dbp5 ATPase activity, and the identification of a novel paradigm for regulation of Dbp5 by Nup159. Based on in vitro biochemical assays, X-ray crystallography, and corresponding in vivo phenotypes, we propose here an updated model of the Dbp5 cycle during mRNP export through the NPC. This takes into account all available data and provides a platform for future studies.