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输出的核内事件的理解大大增加。我能够通过证明mRNA通过核孔复合体输出在功能上和物理上与转录延伸过程偶联来为当前模型做出贡献（Sträßer等人（2000），JCB; Sträßer和Hurt（2000），EMBO J; Sträßer和Hurt（2001），Nature; Sträßer等人（2002），Nature）。这种偶联是由一种名为TREX的蛋白质复合物介导的，该蛋白质复合物由在转录延伸和mRNA输出中起作用的蛋白质组成。TREX的亚复合物THO复合物在转录延伸中起作用，并且存在于活跃转录的基因上。在这个项目的过程中，我将专注于转录和mRNA输出之间的耦合。具体来说，我想确定的组件，介导的THO复合物与转录机器在延长生物化学和遗传学方法的相互作用。我将解决如何THO被招募到一个活跃的转录基因，以及转录起始如何耦合到mRNA的出口。此外，我将描述Gbp 2，Hrb 1和Tex 1的功能，这三种蛋白质的TREX复合物，其中知之甚少。我希望这些研究的结果将大大促进我们对mRNA生物合成中非常早期的事件与其向细胞质的输出过程的理解。

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.