PDF(Pubmed)
Abstract：
In yeast Saccharomyces cerevisiae, there are two translation termination factors, eRF1 (Sup45) and eRF3 (Sup35), which are essential for viability. Previous studies have revealed that presence of nonsense mutations in these genes leads to amplification of mutant alleles (sup35-n and sup45-n), which appears to be necessary for the viability of such cells. However, the mechanism of this phenomenon remained unclear. In this study, we used RNA-Seq and proteome analysis to reveal the complete set of gene expression changes that occur during cellular adaptation to the introduction of the sup35-218 nonsense allele. Our analysis demonstrated significant changes in the transcription of genes that control the cell cycle: decreases in the expression of genes of the anaphase promoting complex APC/C (APC9, CDC23) and their activator CDC20, and increases in the expression of the transcription factor FKH1, the main cell cycle kinase CDC28, and cyclins that induce DNA biosynthesis. We propose a model according to which yeast adaptation to nonsense mutations in the translation termination factor genes occurs as a result of a delayed cell cycle progression beyond the G2-M stage, which leads to an extension of the S and G2 phases and an increase in the number of copies of the mutant sup35-n allele.
摘要：
在酿酒酵母中，有两个翻译终止因素，eRF1(Sup45)和eRF3(Sup35)，这对生存能力至关重要。先前的研究表明，这些基因中无义突变的存在会导致突变等位基因（sup35-n和sup45-n）的扩增，这似乎是这种细胞存活所必需的。然而,这种现象的机制尚不清楚。在这项研究中,我们使用RNA-Seq和蛋白质组分析揭示了在细胞适应sup35-218无义等位基因引入过程中发生的全套基因表达变化。我们的分析表明，控制细胞周期的基因转录发生了显着变化：后期促进复合物APC/C（APC9，CDC23）及其激活剂CDC20的基因表达减少，转录因子FKH1的表达增加，主要的细胞周期激酶CDC28和诱导DNA生物合成的细胞周期蛋白。我们提出了一个模型，根据该模型，酵母对翻译终止因子基因中的无义突变的适应是由于细胞周期进程延迟超过G2-M阶段而发生的。这导致S和G2期的扩展以及突变体sup35-n等位基因的拷贝数增加。
