Functions of transcription elongation factor S-II for cell stress response and development

S-II最初被鉴定为体外RNA聚合酶II的刺激因子。我们研究这种蛋白质的生物学已有30多年了。目前，S-II被认为是一种普遍存在于真核细胞中的转录延伸因子。许多研究人员正在研究S-II在真核生物转录中的作用。研究表明，5-11在真核细胞的转录调控中起着重要作用。然而，没有直接的证据支持这一观点。这个项目的目的是为了验证一个假设。S-II在细胞氧化应激反应中起作用。我们还假设S-II对发育至关重要。我们用同源重组技术检测了S-II基因缺失的酵母细胞和小鼠的表型。我们发现酵母S-II基因缺失突变体对氧化应激具有更高的敏感性。我们还证明了突变体的转录保真度下降。氧化应激可引起作为RNA合成底物的核苷酸的氧化。此外，S-II基因缺失突变体的小鼠胚胎在发育早期表现出致死率。我们发现突变体在红细胞分化中表现出异常表型。这些结果支持了我们的假设，即S-II对氧化应激耐受性很重要，对个体身体的发育至关重要。

S-II was originally identified as a stimulatory factor of RNA polymerase II in vitro. We have been studying biology of this protein for more than 30 years. Nowadays, S-II is recognized as a transcription elongation factor ubiquitously present in eukaryotic cells. A number of researchers are now studying a role of S-II in eukaryotic transcription. It has been proposed that 5-11 plays an important role on the regulation of transcription in eukaryotic cells. However, there is no direct evidence supporting this notion.The purpose of this project was to test a hypothesis that. S-II plays a role in oxidative stress response in cells. We also hypothesized that S-II is essential for development. We examined phenotypes of yeast cells and mice whose S-II genes were deleted by homologous recombination technique. We showed that yeast deletion mutant of the S-II gene showed higher sensitivity to oxidative stress. We also demonstrated that fidelity of transcription decreased in the mutant. Oxidative stress may cause oxidization of nucleotides that are substrates for RNA synthesis. Furthermore, embryos of mice deletion mutant of the S-II gene showed lethality at early stage of development. We found that the mutant showed abnormal phenotype in erythro differentiation. These results supports our hypothesis that S-II is important for tolerance to oxidative stress and is essential for development of individual bodies.