A dynamic transcriptional network communicates growth potential to ribosome synthesis and critical cell size

Paul Jorgensen, Ivan Rupeš, Jeffrey R. Sharom, Lisa Schneper, James R. Broach, Mike Tyers

Research output: Contribution to journalArticle

431 Citations (Scopus)

Abstract

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 AP 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.

Original languageEnglish (US)
Pages (from-to)2491-2505
Number of pages15
JournalGenes and Development
Volume18
Issue number20
DOIs
StatePublished - Oct 15 2004

Fingerprint

Gene Regulatory Networks
Ribosomes
Cell Size
Ribosomal Proteins
Growth
Food
Regulon
Saccharomycetales
G1 Phase
Starvation
Genes
Saccharomyces cerevisiae
Cell Cycle
Homeostasis
Carbon

All Science Journal Classification (ASJC) codes

  • Genetics
  • Developmental Biology

Cite this

Jorgensen, Paul ; Rupeš, Ivan ; Sharom, Jeffrey R. ; Schneper, Lisa ; Broach, James R. ; Tyers, Mike. / A dynamic transcriptional network communicates growth potential to ribosome synthesis and critical cell size. In: Genes and Development. 2004 ; Vol. 18, No. 20. pp. 2491-2505.
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A dynamic transcriptional network communicates growth potential to ribosome synthesis and critical cell size. / Jorgensen, Paul; Rupeš, Ivan; Sharom, Jeffrey R.; Schneper, Lisa; Broach, James R.; Tyers, Mike.

In: Genes and Development, Vol. 18, No. 20, 15.10.2004, p. 2491-2505.

Research output: Contribution to journalArticle

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