Berger Axel B, Decourty Laurence, Badis Gwenaël, Nehrbass Ulf, Jacquier Alain, Gadal Olivier
Unité de Biologie Cellulaire du Noyau, Unité de Génétique des Interactions Macromoléculaires, CNRS URA 2171, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris cedex 15, France.
Mol Cell Biol. 2007 Nov;27(22):8015-26. doi: 10.1128/MCB.01102-07. Epub 2007 Sep 17.
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.
核糖体生物合成需要等摩尔量的四种核糖体RNA(rRNA)和所有79种核糖体蛋白(RP)。真核生物RNA聚合酶(Pol)I、III和II对rRNA和RP合成的协调调控是生长控制的关键要求。我们采用一种全新的全局遗传方法表明,当Hmo1缺失与RNA Pol II或Pol I转录机制的组分、特定RP或TOR信号通路的突变相结合时会变得致命。Hmo1直接与Pol I转录的区域以及一部分RP基因启动子相互作用。Hmo1表达的下调会影响RP基因的表达。在TORC1受到抑制时,Hmo1会同时从核糖体DNA(rDNA)和一些RP基因启动子上解离。最后,在没有Hmo1的情况下,TOR对RP基因的抑制作用会得到缓解。因此,我们在此表明,酿酒酵母Hmo1在TOR信号通路的控制下直接参与协调Pol I对rDNA的转录以及Pol II对RP基因的表达。