Regulation of ribosome biogenesis by the rapamycin-sensitive TOR-signaling pathway in Saccharomyces cerevisiae

Regulation of ribosome biogenesis by the rapamycin-sensitive TOR-signaling pathway in Saccharomyces cerevisiae
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DOI:
10.1091/mbc.10.4.987
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发表时间:
1999-04-01
影响因子:
3.3
通讯作者:
Walter, P
Walter, P
中科院分区:
生物学3区
文献类型:
--
作者:
Powers, T;Walter, P

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TOR (target of rapamycin)信号转导通路是所有真核细胞控制细胞生长的重要机制。具体来说,TOR信号根据营养物质的可用性调节细胞的蛋白质生物合成能力。在哺乳动物细胞中,该途径的一个分支控制一般的翻译起始,而另一个分支专门调节核糖体蛋白(r-蛋白)mrna的翻译。在酿酒酵母中,TOR通路类似地调控一般的翻译起始,但其在核糖体成分合成中的具体作用尚不清楚。在这里,我们证明在酵母中,通过TOR途径控制核糖体的生物合成是非常复杂的。除了对翻译起始的一般影响外,TOR对r-蛋白基因的转录以及35S前体rRNA的合成和后续加工具有强烈的控制作用。我们还发现TOR信号是诱导r蛋白基因转录的先决条件,这种转录发生在对改善的营养条件的反应中。这种诱导先前已被证明涉及ras -腺苷酸环化酶和可发酵生长介质诱导的途径,因此我们的结果表明这三种途径可能密切相关。
The TOR (target of rapamycin) signal transduction pathway is an important mechanism by which cell growth is controlled in all eucaryotic cells. Specifically, TOR signaling adjusts the protein biosynthetic capacity of cells according to nutrient availability. Ln mammalian cells, one branch of this pathway controls general translational initiation, whereas a separate branch specifically regulates the translation of ribosomal protein (r-protein) mRNAs. In Saccharomyces cerevisiae, the TOR pathway similarly regulates general translational initiation, but its specific role in the synthesis of ribosomal components is not well understood. Here we demonstrate that in yeast control of ribosome biosynthesis by the TOR pathway is surprisingly complex. in addition to general effects on translational initiation, TOR exerts drastic control over r-protein gene transcription as well as the synthesis and subsequent processing of 35S precursor rRNA. We also find that TOR signaling is a prerequisite for the induction of r-protein gene transcription that occurs in response to improved nutrient conditions. This induction has been shown previously to involve both the Ras-adenylate cyclase as well as the fermentable growth medium-induced pathways, and our results therefore suggest that these three pathways may be intimately linked.