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Target of rapamycin (TOR) signaling coordinatestRNA and 5S rRNA gene transcription with growthrate in yeast

机译:雷帕霉素(TOR)信号转导靶标tRNA和5S rRNA基因在酵母中的生长速率

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Transcriptional regulation of genes encoding ribosomal proteins, translation factors, ribosomal RNAs, and the tRNAs plays a critical role in cellular physiology by modulating the availability of key components of the protein synthetic machinery according to the need for cell growth. Recent work in yeast and mammalian systems has revealed that the target of rapamycin (TOR) signaling pathway functions in setting the translational output of the cell in response to nutrient/growth factor availability. The central components of the TOR pathway are the TOR kinases, which are inhibited by the macrolide antibiotic rapamycin. Using yeast as a model system we have tested if the control of translation by the TOR kinases includes an effect on transcription of two components of the translational apparatus, 5S rRNA and the tRNAs. Biochemical studies reveal that polymerase (pol) III transcription of the 5S rRNA and the tRNA genes is regulated by TOR signaling in yeast. Interference with TOR signaling inhibits the activity of RNA pol III and likely TFIIIB, core components of the pol III transcriptional machinery. The mechanism of inhibition involves an effect that is independent of the repression of translation that results when TOR signaling is impaired. We propose that the TOR kinases are components of a signaling network that ensures appropriate expression of the protein synthetic machinery under different growth conditions.Considering the conservation of the TOR pathway and the pol III transcription machinery between yeast and human, this regulatory mechanism is likely to be conserved in eukaryotes.
机译:编码核糖体蛋白,翻译因子,核糖体RNA和tRNA的基因的转录调控,根据细胞生长的需要,通过调节蛋白质合成机制的关键成分的可用性,在细胞生理学中起着至关重要的作用。酵母和哺乳动物系统中的最新工作表明,雷帕霉素(TOR)信号转导通路的靶标在响应营养/生长因子可用性而设置细胞的翻译输出中起作用。 TOR途径的主要成分是TOR激酶,该激酶被大环内酯类抗生素雷帕霉素抑制。使用酵母作为模型系统,我们已经测试了TOR激酶对翻译的控制是否包括对翻译设备5S rRNA和tRNA的两个成分的转录的影响。生化研究表明,酵母中TOR信号调节5S rRNA和tRNA基因的聚合酶(pol)III转录。干扰TOR信号会抑制RNA pol III的活性,并可能抑制pol III转录机制的核心成分TFIIIB。抑制机制涉及一种独立于TOR信号转导时导致的翻译抑制的效应。我们认为TOR激酶是信号转导网络的组成部分,可确保蛋白质合成机制在不同生长条件下的正确表达。考虑到TOR途径的保守性以及酵母与人之间pol III转录机制的保守性,这种调节机制可能会被保存在真核生物中。

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