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. Overall design: RNA-seq dataset of wild-type and Rph1 deletion yeast treated with or without rapamycin. ChIP-seq dataset of Pol II and FLAG-Rph1 treated with or without rapamycin.