1. Department of Molecular Biology and NCCR Program 'Frontiers in Genetics' University of Geneva, Sciences III, 30, quai Ernest-Ansermet, Geneva 4, CH-1211, Switzerland
2. Service de Biochimie et Génétique Moléculaire, CEA Saclay, 91191 Gif-Sur-Yvette, Cedex, France

Correspondence to: David Shore¹ Email: David.Shore@molbio.unige.ch

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 conditions^{2, 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.

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