Coupling of transcription to mRNA export

在真核细胞中，mRNA从细胞核输出到细胞质是基因表达所必需的。在过去的几年里，我们对mRNA输出的核内事件的了解有了很大的提高。我能够对目前的模型做出贡献，因为我证明了通过核孔复合体输出的mRNA在功能上和物理上与转录延伸过程相耦合(Sträçer等人)。(2000年)，JCB；斯特拉伯和赫特(2000年)，EMBO J；斯特拉伯和赫特(2001年)，自然；斯特拉伯等人。(2002)，《自然》)。这种偶联是由一种名为TREX的蛋白质复合体介导的，该复合体由参与转录延伸和mRNA输出的蛋白质组成。TREX的一个亚复合体，THO复合体，在转录延伸中发挥作用，并存在于活跃转录的基因上。在拟议的项目过程中，我将重点讨论转录和信使核糖核酸输出之间的耦合。具体地说，我想通过生化和遗传方法确定在伸长过程中介导Tho复合体与转录机制相互作用的组件。我将讲述Tho是如何被招募到一个活跃的转录基因上的，以及转录启动是如何耦合到mRNA输出的。此外，我还将描述GbP2、Hrb1和Tex1的功能，这三种蛋白质是TREX复合体中的三种蛋白质，人们对它们知之甚少。我希望这些拟议研究的结果将极大地促进我们对mRNA生物发生的早期事件与其输出到细胞质的过程的理解。

In a eukaryotic cell, mRNA export from the nucleus to the cytoplasm is essential for gene expression. In the past couple of years, our understanding of the intranuclear events of mRNA export has increased immensely. I was able to contribute to the current model by demonstrating that mRNA export through the nuclear pore complexes is functionally and physically coupled to the process of transcription elongation (Sträßer et al. (2000), JCB; Sträßer and Hurt (2000), EMBO J; Sträßer and Hurt (2001), Nature; Sträßer et al. (2002), Nature). This coupling is mediated by a protein complex named TREX, which consists of proteins with roles in transcription elongation and mRNA export. A subcomplex of TREX, the THO complex, functions in transcription elongation and is present on actively transcribed genes. During the course of the proposed project, I will focus on the coupling between transcription and mRNA export. Specifically, I want to identify components that mediate the interaction of the THO complex with the transcription machinery during elongation by biochemical and genetic approaches. I will address how THO is recruited to an actively transcribed gene and how transcription initiation is coupled to mRNA export. In addition, I will characterize the function of Gbp2, Hrb1, and Tex1, three proteins of the TREX complex about which very little is known. I expect that the results from these proposed studies will significantly advance our understanding of the processes that couple very early events in mRNA biogenesis to its export to the cytoplasm.