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Modulation of Yeast Genome Expression in Response to Defective RNA Polymerase III-Dependent Transcription

机译:酵母基因组表达对有缺陷的RNA聚合酶III依赖转录的响应的调制。

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We used genome-wide expression analysis in Saccharomyces cerevisiae to explore whether and how the expression of protein-coding, RNA polymerase (Pol) II-transcribed genes is influenced by a decrease in RNA Pol III-dependent transcription. The Pol II transcriptome was characterized in four thermosensitive, slow-growth mutants affected in different components of the RNA Pol III transcription machinery. Unexpectedly, we found only a modest correlation between altered expression of Pol II-transcribed genes and their proximity to class III genes, a result also confirmed by the analysis of single tRNA gene deletants. Instead, the transcriptome of all of the four mutants was characterized by increased expression of genes known to be under the control of the Gcn4p transcriptional activator. Indeed, GCN4 was found to be translationally induced in the mutants, and deleting the GCN4 gene eliminated the response. The Gcn4p-dependent expression changes did not require the Gcn2 protein kinase and could be specifically counteracted by an increased gene dosage of initiator tRNAMet. Initiator tRNAMet depletion thus triggers a GCN4-dependent reprogramming of genome expression in response to decreased Pol III transcription. Such an effect might represent a key element in the coordinated transcriptional response of yeast cells to environmental changes.
机译:我们在啤酒酵母(Saccharomyces cerevisiae)中使用了全基因组表达分析,以研究是否以及如何减少RNA聚合酶III依赖性转录对蛋白质编码RNA聚合酶(Pol)II转录基因的表达的影响。 Pol II转录组的特征是受四个热敏,缓慢生长的突变体影响,这些突变体受RNA Pol III转录机制的不同组成部分影响。出乎意料的是,我们发现Pol II转录基因的表达变化与它们与III类基因的接近程度之间只有适度的相关性,这一结果也通过对单个tRNA基因缺失子的分析得到了证实。取而代之的是,所有四个突变体的转录组都以已知在Gcn4p转录激活因子控制下的基因表达增加为特征。确实,在突变体中发现了 GCN4 的翻译诱导,删除 GCN4 基因消除了应答。 Gcn4p依赖的表达变化不需要Gcn2蛋白激酶,并且可以通过增加启动子tRNA Met 的基因剂量来专门抵消。引发剂tRNA Met 的耗竭因此会触发响应于Pol III转录降低的 GCN4 依赖的基因组表达重编程。这种作用可能是酵母细胞对环境变化的协调转录反应中的关键因素。

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