Coordinated regulation of ribosomal RNA (rRNA) synthesis and ribosomal protein gene (RPG) transcription by eukaryotic RNA polymerases (RNAP) is a key requirement for growth control. Although evidence for balance between RNPI-dependent 35S rRNA production and RNAPII-mediated RPG transcription have been described, the molecular basis is still obscure. Here, we found that Rph1 modulates the transcription status of both rRNAs and RPGs in yeast. We show that Rph1 widely associates with RNAPI and RNAPII-transcribed genes. Deletion of RPH1 remarkably alleviates cell slow growth caused by TORC1 inhibition via derepression of rRNA and RPG transcription under nutrient stress conditions. Mechanistically, Rim15 kinase phosphorylates Rph1 upon rapamycin treatment. Phosphorylation-mimetic mutant of Rph1 exhibited more resistance to rapamycin treatment, decreased association with ribosome-related genes, and faster cell growth compared to the wild-type, indicating that Rph1 dissociation from chromatin ensures cell survival upon nutrient stress. Our results uncover the role of Rph1 in coordination of RNA polymerases-mediated transcription to control cell growth under nutrient stress conditions.

中文翻译：

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Rph1协调核糖体蛋白基因和核糖体RNA的转录，以控制营养胁迫条件下的细胞生长。

真核RNA聚合酶（RNAP）对核糖体RNA（rRNA）合成和核糖体蛋白基因（RPG）转录的协调调节是生长控制的关键要求。尽管已描述了RNPI依赖性35S rRNA产生与RNAPII介导的RPG转录之间平衡的证据，但分子基础仍然不清楚。在这里，我们发现Rph1调节酵母中rRNA和RPG的转录状态。我们显示，Rph1与RNAPI和RNAPII转录的基因广泛关联。RPH1的删除在营养胁迫条件下，通过抑制rRNA和RPG转录，可显着缓解TORC1抑制引起的细胞缓慢生长。从机理上讲，雷帕霉素处理后，Rim15激酶使Rph1磷酸化。与野生型相比，Rph1的磷酸化模拟突变体对雷帕霉素处理表现出更大的抗性，与核糖体相关基因的结合减少，并且细胞生长更快，表明Rph1与染色质的解离确保了营养胁迫下的细胞存活。我们的结果揭示了Rph1在RNA聚合酶介导的转录调控中在营养胁迫条件下控制细胞生长的作用。