Jimeno S, Rondón A G, Luna R, Aguilera A
Departamento de Genética, Facultad de Biología, Universidad de Sevilla, 41012 Sevilla, Spain.
EMBO J. 2002 Jul 1;21(13):3526-35. doi: 10.1093/emboj/cdf335.
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 hpr1 Delta. 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.
THO复合体是一种包含四种多肽（Tho2、Hpr1、Mft1和Thp2）的多聚体因子。编码THO的任何一个基因发生突变都会导致转录受损以及转录依赖性的高重组表型，这表明THO在基因表达中具有功能性作用。利用为研究长的富含G+C的DNA序列的表达而开发的体内检测方法，我们分离出了SUB2，一个参与mRNA剪接和输出的基因，作为hpr1 Delta基因表达缺陷的多拷贝抑制子。对mRNA代谢与THO之间假定的功能关系的进一步研究表明，mRNA输出突变体sub2、yra1、mex67和mtr2具有与THO突变体相似的缺陷转录和高重组表型。此外，在Mex67 mRNA输出缺陷的细胞中，THO变得至关重要。最后，我们已经证明THO在体外具有与RNA和DNA结合的能力。这些结果表明，由THO和mRNA输出蛋白介导的新生mRNA延伸和代谢过程之间存在功能联系，这对基因组稳定性的维持具有重要意义。
