Rph1 coordinates transcription of ribosomal protein genes and ribosomal RNAs to control cell growth under nutrient stress conditions

Nucleic Acids Res. 2020 Sep 4;48(15):8360-8373. doi: 10.1093/nar/gkaa558.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Proliferation / genetics*
  • Chromatin / genetics
  • Gene Expression Regulation, Fungal / genetics
  • Histone Demethylases / genetics*
  • Phosphorylation
  • Protein Kinases / genetics*
  • RNA, Ribosomal / genetics*
  • Repressor Proteins / genetics*
  • Ribosomal Proteins / genetics
  • Ribosomes / genetics
  • Ribosomes / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / genetics*
  • Signal Transduction / genetics
  • Transcription, Genetic

Substances

  • Chromatin
  • RNA, Ribosomal
  • RPH1 protein, S cerevisiae
  • Repressor Proteins
  • Ribosomal Proteins
  • Saccharomyces cerevisiae Proteins
  • Histone Demethylases
  • Protein Kinases
  • Rim15 protein, S cerevisiae