Rph1 coordinates transcription of ribosomal protein gene and ribosomal RNA to control cell growth under nutrient stress conditions

Coordinated regulation of ribosomal RNA (rRNA) and ribosomal protein gene (RPG) transcription by eukaryotic RNA polymerases (RNAP) is a key requirement for growth control. Although evidence for balance between RNPI-mediated 35S rRNA production and RNAPII-mediated RPG transcription have been described, the molecular basis is obscure. Here, we found that Rph1 modulates the transcription status of both rRNA and RPG 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. Phosphorylationmimetic 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.真核生物RNA聚合酶（RNA polymerases, RNAP）对核糖体RNA（ribosomal RNA, rRNA）和核糖体蛋白基因（ribosomal protein gene, RPG）转录的协同调控，是细胞生长调控的核心要件。尽管已有研究报道RNA聚合酶I（RNA polymerase I, RNAPI）介导的35S rRNA生成与RNA聚合酶II（RNA polymerase II, RNAPII）介导的RPG转录之间存在平衡现象，但其分子机制仍不明晰。本研究发现，酵母中的Rph1可调控rRNA与RPG的转录状态。我们证实，Rph1可广泛结合由RNAPI与RNAPII转录的基因。在营养胁迫条件下，敲除RPH1可通过解除rRNA与RPG的转录抑制，显著缓解由雷帕霉素靶蛋白复合物1（TORC1）抑制引发的细胞生长迟缓。机制上，雷帕霉素处理后，Rim15激酶可磷酸化Rph1。与野生型菌株相比，Rph1的磷酸化模拟突变体表现出更强的雷帕霉素抗性、与核糖体相关基因的结合能力减弱，且细胞生长速度更快，这表明Rph1从染色质上解离可确保细胞在营养胁迫下存活。本研究揭示了Rph1在协同调控RNA聚合酶介导的转录以控制营养胁迫下细胞生长过程中的作用。