The yeast THO complex and mRNA export factors link RNA metabolism with transcription and genome instability
The yeast THO complex and mRNA export factors link RNA metabolism with transcription and genome instability
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DOI：
10.1093/emboj/cdf335
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发表时间：
2002-07-01
期刊：
影响因子：
11.4
通讯作者：
Aguilera, A
中科院分区：
文献类型：
--
作者：
Jimeno, S;Rondón, AG;Aguilera, A
THO复合物是一种多聚体因子，含有四种多肽Tho 2、Hpr 1、Mft 1和Thp 2。任何编码THO的基因突变都会导致转录受损和转录依赖性超重组表型，表明THO在基因表达中具有功能性作用。使用在体内试验开发的研究表达的长和G+ C-丰富的DNA序列，我们已经分离出SUB 2，一个基因参与mRNA剪接和出口，作为一个多拷贝抑制基因表达缺陷的hpr 1Delta。进一步研究mRNA代谢和THO之间的假定功能关系发现，mRNA输出突变体sub 2，yra 1，mex 67和mtr 2具有与THO突变体相似的转录缺陷和超重组表型。此外，THO在具有缺陷性Mex 67 mRNA输出的细胞中变得必不可少。最后，我们已经表明，THO具有与RNA和DNA在体外的能力。这些结果表明THO和mRNA输出蛋白介导的新生mRNA的伸长和代谢过程之间存在功能联系，这对维持基因组稳定性具有重要影响。
The THO complex is a multimeric factor containing four polypeptides, Tho2, Hpr1, Mft1 and Thp2. Mutations in any of the genes encoding THO confer impairment of transcription and a transcription-dependent hyper-recombination phenotype, suggesting that THO has a functional role in gene expression. Using an in vivo assay developed to study expression of long and G+C-rich DNA sequences, we have isolated SUB2, a gene involved in mRNA splicing and export, as a multicopy suppressor of the gene expression defect of hpr1Delta. Further investigation of a putative functional relationship between mRNA metabolism and THO revealed that mRNA export mutants sub2, yra1, mex67 and mtr2 have similar defective transcription and hyper-recombination phenotypes as THO mutants. In addition, THO becomes essential in cells with a defective Mex67 mRNA export er. Finally, we have shown that THO has the ability to associate with RNA and DNA in vitro. These results indicate a functional link between the processes of elongation and metabolism of nascent mRNA mediated by THO and mRNA export proteins, which have important consequences for the maintenance of genome stability.