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Dbp5, Glel-IP_6 and Nup159 A working model for mRNP export

机译：Dbp5，Glel-IP_6和Nup159 mRNP导出的工作模型

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摘要

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 Glel bound to inositol hexakisphosphate (IP_6) 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 mech-anism of Dbp5 RNP remodeling, the role of Glel-IP_6 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.
机译：基因表达是一个逐步的过程，涉及独特的细胞过程，包括转录，mRNA（mRNA）处理，mRNA输出和翻译。随着mRNA的合成，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穿过基因表达的不同步骤而变化，并且在这些事件中起关键作用。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，在此处，与肌醇六磷酸（IP_6）结合的输出蛋白Glel在空间上激活了DEAD-box蛋白Dbp5的ATP水解和mRNP重塑活性。 。我们实验室和其他实验室的最新工作为Dbp5的功能和调节提供了重要见解。这些包括对Dbp5 RNP重塑的机制的更详细的解释，Glel-IP_6在刺激Dbp5 ATPase活性中的作用以及由Nup159鉴定调控Dbp5的新范例。基于体外生化分析，X射线晶体学和相应的体内表型，我们在这里提出了在mRNP通过NPC导出过程中Dbp5循环的更新模型。这将考虑所有可用数据，并为将来的研究提供平台。

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