Growth-regulated recruitment of the essential yeast ribosomal protein gene activator Ifh1

Stephan B. Schawalder, Mehdi Kabani, Isabelle Howald, Urmila Choudhury, Michel Werner and David Shore ()
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Stephan B. Schawalder: Department of Molecular Biology and NCCR Program ‘Frontiers in Genetics’ University of Geneva, Sciences III
Mehdi Kabani: CEA Saclay
Isabelle Howald: Department of Molecular Biology and NCCR Program ‘Frontiers in Genetics’ University of Geneva, Sciences III
Urmila Choudhury: Department of Molecular Biology and NCCR Program ‘Frontiers in Genetics’ University of Geneva, Sciences III
Michel Werner: CEA Saclay
David Shore: Department of Molecular Biology and NCCR Program ‘Frontiers in Genetics’ University of Geneva, Sciences III

Nature, 2004, vol. 432, issue 7020, 1058-1061

Abstract: Abstract Regulation of ribosome biogenesis is central to the control of cell growth1. In rapidly growing yeast cells, ribosomal protein (RP) genes account for approximately one-half of all polymerase II transcription-initiation events1, yet these genes are markedly and coordinately downregulated in response to a number of environmental stress conditions2,3,4, or during the transition from fermentation to respiration5. Although several conserved signalling pathways (TOR, RAS/protein kinase A and protein kinase C) impinge upon RP gene transcription1, little is known about how initiation at these genes is controlled. Rap1 (refs 6, 7) and more recently Fhl1 (ref. 8) were shown to bind upstream of many RP genes. Here we show that the essential protein Ifh1 binds to and activates many RP gene promoters under optimal growth conditions in Saccharomyces cerevisiae. Ifh1 is recruited to RP gene promoters through the forkhead-associated domain of Fhl1. Ifh1 binding decreases when RP genes are downregulated either by TOR inhibition or nutrient depletion, and is restored after release from starvation or upon regulated induction of IFH1 expression. These findings indicate a central role for Ifh1 and Fhl1 in RP gene regulation.

Date: 2004
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DOI: 10.1038/nature03200

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