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首页> 外文期刊>The Journal of biological chemistry >The AMP-activated Protein Kinase Snf1 Regulates Transcription Factor Binding, RNA Polymerase II Activity, and mRNA Stability of Glucose-repressed Genes in Saccharomyces cerevisiae
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The AMP-activated Protein Kinase Snf1 Regulates Transcription Factor Binding, RNA Polymerase II Activity, and mRNA Stability of Glucose-repressed Genes in Saccharomyces cerevisiae

机译：AMP活化蛋白激酶SNF1调节葡萄糖抑制基因的转录因子结合，RNA聚合酶II活性和mRNA稳定性在酿酒酵母中的葡萄糖 - 抑制基因

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AMP-activated protein kinase, the “energy sensor of the cell,” responds to low cellular energy stores by regulating enzymes and transcription factors that allow the cell to adapt to limiting nutritional conditions. Snf1, the yeast ortholog of AMP-activated protein kinase, has an essential role in respiratory metabolism in Saccharomyces cerevisiae that includes activating the transcription factor Adr1. How Snf1 regulates Adr1 activity is poorly understood. We used an analog-sensitive allele, SNF1as(I132G), that is inhibited by 2-naphthylmethyl pyrazolopyrimidine 1 to study the role of Snf1 in transcriptional regulation of glucose-repressible genes. When Snf1as was inhibited at the time of glucose depletion, there was a promoter-specific response with some Snf1-dependent genes being activated by low levels of inhibitor, whereas all Snf1-dependent genes were inhibited at high levels. Transcript accumulation was more sensitive to Snf1as inhibition than Adr1 or RNA polymerase (pol) II binding or acetylation of promoter nucleosomes. When Snf1as was inhibited after gene activation, Adr1 and RNA pol II remained at promoters, and RNA pol II remained in the ORF with associated nascent transcripts. However, cytoplasmic mRNAs were lost at a rapid rate compared with their decay following chemical or genetic inactivation of RNA pol II. In conclusion, Snf1 appears to affect multiple steps in gene regulation, including transcription factor binding, RNA polymerase II activity, and cytoplasmic mRNA stability.
机译：AMP活化蛋白激酶是“细胞的能量传感器”，通过调节酶和转录因子来响应低细胞能量储存，使细胞适应营养状况。 SNF1，AMP活化蛋白激酶的酵母直向经理，具有在糖酵母酿酒酵母中的呼吸代谢中具有重要作用，包括激活转录因子ADR1。 SNF1如何调节ADR1活动知之甚少。我们使用了模拟敏感等位基因，SNF1As（I132G），其被2-萘甲基吡唑氮杂嘧啶1抑制，研究了SNF1在葡萄糖 - 可抑制基因的转录调节中的作用。当在葡萄糖耗尽时抑制SNF1As时，具有通过低水平的抑制剂激活的一些SNF1依赖性基因的启动子特异性响应，而所有SNF1依赖性基因抑制在高水平。转录物累积比ADR1或RNA聚合酶（POL）II结合或启动子核肉的乙酰化更敏感。当在基因激活后抑制SNF1As时，ADR1和RNA POL II仍然在启动子上，并且RNA POL II残留在具有相关的新生转录物的ORF中。然而，与RNA POL II的化学或遗传失活后，以快速速率损失细胞质MRNA。总之，SNF1似乎影响基因调控中的多个步骤，包括转录因子结合，RNA聚合酶II活性和细胞质mRNA稳定性。

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