Modulation of yeast genome expression in response to defective RNA polymerase III-dependent transcription
Modulation of yeast genome expression in response to defective RNA polymerase III-dependent transcription
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DOI：
10.1128/mcb.25.19.8631-8642.2005
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发表时间：
2005-10-01
影响因子：
5.3
通讯作者：
Dieci, G
中科院分区：
文献类型：
--
作者：
Conesa, C;Ruotolo, R;Dieci, G
我们在酿酒酵母中使用全基因组表达分析来探索蛋白质编码、RNA聚合酶（Pol）II转录基因的表达是否以及如何受到RNA Pol III依赖性转录减少的影响。Pol II转录组的特点是在四个温度敏感，生长缓慢的突变体中的RNA Pol III转录机制的不同组成部分的影响。出乎意料的是，我们发现改变Pol II转录基因的表达与其接近III类基因之间只有适度的相关性，这一结果也通过对单个tRNA基因缺失体的分析得到证实。相反，所有四种突变体的转录组的特征在于已知在Gcn4p转录激活因子控制下的基因的表达增加。事实上，发现GCN 4在突变体中被诱导，并且删除GCN 4基因消除了反应。Gcn4p依赖的表达变化不需要Gcn2蛋白激酶，并且可以通过增加起始tRNA（Met）的基因剂量来特异性地抵消。因此，启动子tRNA（Met）耗竭触发了GCN 4依赖性的基因组表达重编程，以响应Pol III转录的降低。这种效应可能代表了酵母细胞对环境变化的协调转录反应中的一个关键因素。
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 tRNA(Met). Initiator tRNA(Met) 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.