A dynamic transcriptional network communicates growth potential to ribosome synthesis and critical cell size
A dynamic transcriptional network communicates growth potential to ribosome synthesis and critical cell size
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DOI：
10.1101/gad.1228804
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发表时间：
2004-10-15
影响因子：
10.5
通讯作者：
Tyers, M
中科院分区：
文献类型：
--
作者：
Jorgensen, P;Rupes, I;Tyers, M
细胞大小的动态平衡需要生长和分裂之间的基本平衡。芽殖酵母酿酒酵母（Saccharomyces cerevisiae）通过在G1期晚期的细胞周期定型（Start）之前强制生长到临界细胞大小来建立这种平衡。营养物调节临界大小阈值，使得细胞在富培养基中大而在贫培养基中小。在这里，我们表明，启动，Sfp 1和Sch 9，是两个有效的负调节激活的核糖体蛋白（RP）和核糖体生物合成（Ribi）调节子，转录程序，决定核糖体合成速率在雅阁环境和细胞内条件。Sfp 1和Sch 9是碳源调节细胞大小所必需的，分别在核定位和丰度水平上受到调节。Sfp 1核浓度对营养和胁迫条件反应迅速，并受到Ras/PKA和TOR信号通路的调节。反过来，Sfp 1影响Fhl 1和Ifh 1的核定位，其结合RP基因启动子。饥饿或缺乏Sfp 1导致Fhl 1和Ifh 1定位于核仁区域，伴随着RP基因转录的减少。这些发现表明，营养信号通过Sfp 1和Sch 9介导的核糖体生物合成速率的控制来设定临界细胞大小阈值。
Cell-size homeostasis entails a fundamental balance between growth and division. The budding yeast Saccharomyces cerevisiae establishes this balance by enforcing growth to a critical cell size prior to cell cycle commitment (Start) in late G1 phase. Nutrients modulate the critical size threshold, such that cells are large in rich medium and small in poor medium. Here, we show that two potent negative regulators of Start, Sfp1 and Sch9, are activators of the ribosomal protein (RP) and ribosome biogenesis (Ribi) regulons, the transcriptional programs that dictate ribosome synthesis rate in accord with environmental and intracellular conditions. Sfp1 and Sch9 are required for carbon-source modulation of cell size and are regulated at the level of nuclear localization and abundance, respectively. Sfp1 nuclear concentration responds rapidly to nutrient and stress conditions and is regulated by the Ras/PKA and TOR signaling pathways. In turn, Sfp1 influences the nuclear localization of Fhl1 and Ifh1, which bind to RP gene promoters. Starvation or the absence of Sfp1 causes Fhl1 and Ifh1 to localize to nucleolar regions, concomitant with reduced RP gene transcription. These findings suggest that nutrient signals set the critical cell-size threshold via Sfp1 and Sch9-mediated control of ribosome biosynthetic rates.