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Biochemical and structural analysis of human THO complex that regulates the mRNA synthesis and maturation

调节 mRNA 合成和成熟的人类 THO 复合物的生化和结构分析

基本信息

批准号：
16580073
负责人：
MASUDA Seiji
金额：
$ 2.3万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16580073/
关键词：
transcription elongation mRNA export splicing mRNA 転写核外輸送

项目摘要

mRNA, used as a template for protein synthesis in eukaryotes, is synthesized by RNA polymerase II complex in nucleus and undergoes a multiple process for maturation including capping, splicing and poly-adenylation. Recent lines of evidence indicate that these mRNA maturation process form a extensive network by a number of coupling factors. We found THO complex as a one of these coupling factor. Furthermore, we named the TREX complex as transcription and export coupling complex by combined with THO complex, Sub2 (UAP56 in human) and Yra1 (Aly in human), first one is mainly supposed to act as a transcription elongation and middle and last ones act as export factors. Previous studies indicate that THO complex in yeast directly recruited into transcribing RNA polymerase II elongation complex and THO complex, in turn, recruits Sub2 and Yra1, and thereby couples transcription and export. In this study, we have investigated the characterization and functional analysis of human THO complex. We found, first, human THO complex is composed of six protein components, second, does not affect the mRNA transcription and splicing in contrast to yeast case, and third, is recruited on mRNA during splicing. We, therefore, hypothesized that THO complex recruitment onto mRNA is regulated by the intron in general. This idea is also supported by the finding that intron in yeast gene inhibits the recruitment of THO complex to transcribing pre-mRNA.

mRNA是真核生物中蛋白质合成的模板，由RNA聚合酶II复合物在细胞核中合成，并经历包括加帽、剪接和多聚腺苷酸化的多个成熟过程。最近的证据表明，这些mRNA成熟过程通过许多偶联因子形成广泛的网络。我们发现THO复合物是这些耦合因子之一。将TREX复合物与THO复合物、Sub2（人的UAP56）和Yra1（人的Aly）结合，命名为转录和输出偶联复合物，前者主要起转录延伸作用，而后者起输出作用。以往的研究表明，酵母中的THO复合物直接招募到转录RNA聚合酶II延伸复合物和THO复合物中，进而招募Sub2和Yra1，从而耦合转录和输出。在这项研究中，我们研究了人类THO复合物的表征和功能分析。我们发现，第一，人THO复合物是由六个蛋白质组成，第二，不影响mRNA的转录和剪接，相反，酵母的情况下，第三，在mRNA上招募剪接过程中。因此，我们假设THO复合物在mRNA上的募集一般受内含子的调控。这一观点也得到了酵母基因内含子抑制THO复合物募集转录前体mRNA的发现的支持。