Asr1p, a novel yeast RNA Polymerase II CTD-binding protein signals alcohol stress to the nucleus

细胞将不利条件视为潜在的压力，将其与其他事物一起传达给细胞核，并通过改变转录活性来做出反应。面包酵母酿酒酵母作为一种简单的模式生物来分析酒精胁迫下的信号转导和基因表达调控。酒精对细胞的生理有多种作用。首先，酒精会改变膜结构并使蛋白质变性。为了补偿发酵过程中发生的这种压力情况，酵母细胞以改变的转录活性作出反应。我们已经鉴定出一种新的面包酵母蛋白质，这种蛋白质是在酒精存在的情况下至关重要的生长所必需的，因此可以进行修复或适应过程。Asr1p（酒精敏感RING/PHD指1蛋白）组成性地穿梭于细胞质和细胞核之间，但在酒精胁迫下在细胞核内积累。Asr1p对酒精有特异和可逆的反应，但对饥饿、热、渗透或氧化应激没有反应。与特定的转录因子相比，Asr1p不结合到启动子区域，而是靶向rna -聚合酶II最大亚基Rpb1p的c端结构域（CTD），这是一个对转录活性的调节和整合至关重要的结构域。由于Asr1p是第一个在酒精胁迫下特异性改变其亚细胞定位的酵母蛋白，它为揭示酒精胁迫下酒精诱导的信号事件和转录调控提供了关键。

Cells sense unfavorable conditions as potentially stressful, communicate it among other things to the nucleus and respond to it by altered transcriptional activity. The baker¿s yeast S. cerevisiae serves as a simple model organism to analyse signal transduction and regulation of gene expression in response to alcohol stress. Alcohol has pleiotropic effects on the physiology of the cell. Primarily, alcohol alters the membrane structure and denatures proteins. To compensate this stressful situation that occurs during fermentation, yeast cells respond with altered transcriptional activity. We have identified a novel protein of baker¿s yeast required for vital growth in presence of alcohol and thus for repair or adaptation processes. Asr1p (Alcohol sensitive RING/PHD finger 1 protein) constitutively shuttles between cytoplasm and nucleus but accumulates in the nucleus upon alcohol stress. Asr1p responds specifically and reversibly to alcohol but not to starvation, heat, osmotic or oxidative stress. In contrast to specific transcription factors, Asr1p does not bind to promoter regions but targets the C-terminal domain (CTD) of the largest subunit Rpb1p of RNA-Polymerase II, a domain crucial for regulation and integration of transcriptional activities. Since Asr1p is the first yeast protein reported that changes its subcellular localization specifically upon alcohol stress, it provides a key to unravel alcohol induced signaling events and transcriptional regulation during alcohol stress.