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RESEARCH PAPER
21 Department of Medical Genetics and Microbiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8; 2 Samuel Lunenfeld Research Institute, Toronto, Ontario, Canada M5G 1X5; 3 Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA
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.
[Keywords: Ribosome; nutrients; nucleolus; size; Start]
Received June 4, 2004; revised version accepted August 17, 2004.
Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.1228804.
4 Corresponding author. E-MAIL tyers{at}mshri.on.ca; FAX (416) 586-8869.
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