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Abstract
Ribosome biogenesis requires equimolar amounts of four rRNAs and all 79 ribosomal proteins (RP). Coordinated regulation of rRNA and RP synthesis by eukaryotic RNA polymerases (Pol) I, III, and II is a key requirement for growth control. Using a novel global genetic approach, we showed that the absence of Hmo1 becomes lethal when combined with mutations of components of either the RNA Pol II or Pol I transcription machineries, of specific RP, or of the TOR pathway. Hmo1 directly interacts with both the region transcribed by Pol I and a subset of RP gene promoters. Down-regulation of Hmo1 expression affects RP gene expression. Upon TORC1 inhibition, Hmo1 dissociates from ribosomal DNA (rDNA) and some RP gene promoters simultaneously. Finally, in the absence of Hmo1, TOR-dependent repression of RP genes is alleviated. Therefore, we show here that Saccharomyces cerevisiae Hmo1 is directly involved in coordinating rDNA transcription by Pol I and RP gene expression by Pol II under the control of the TOR pathway.
SUPPLEMENTAL MATERIAL
We thank Christophe Charles for strains YPH500 and CARA and for sharing unpublished data, George P. Livi for the plasmid bearing the TOR1-1 allele, Yoshiko Kikuchi for the plasmid bearing TOM1, Frédéric Devaux for his help in the transcriptome study, Florence Hantraye for the transcriptome normalization procedure, A. Reimann for his help concerning the quantitative PCR, and Y. Henry, M. Mhlanga, K. Bystrincky, and F. Feueurbach-Fournier for critical reading of the manuscript.
A.B.B. was supported by fellowships from the French Ministry of Research and Technology (MNRT) and the German Academic Exchange Service (DAAD). This work was supported by an ATIP grant from CNRS and the Association Nationale pour la Recherche.