A Molecular Titration System Coordinates Ribosomal Protein Gene Transcription with Ribosomal RNA Synthesis

Mol Cell. 2016 Nov 17;64(4):720-733. doi: 10.1016/j.molcel.2016.10.003. Epub 2016 Nov 3.


Cell growth potential is determined by the rate of ribosome biogenesis, a complex process that requires massive and coordinated transcriptional output. In the yeast Saccharomyces cerevisiae, ribosome biogenesis is highly regulated at the transcriptional level. Although evidence for a system that coordinates ribosomal RNA (rRNA) and ribosomal protein gene (RPG) transcription has been described, the molecular mechanisms remain poorly understood. Here we show that an interaction between the RPG transcriptional activator Ifh1 and the rRNA processing factor Utp22 serves to coordinate RPG transcription with that of rRNA. We demonstrate that Ifh1 is rapidly released from RPG promoters by a Utp22-independent mechanism following growth inhibition, but that its long-term dissociation requires Utp22. We present evidence that RNA polymerase I activity inhibits the ability of Utp22 to titrate Ifh1 from RPG promoters and propose that a dynamic Ifh1-Utp22 interaction fine-tunes RPG expression to coordinate RPG and rRNA transcription.

Keywords: CURI complex; Ifh1; Saccharomyces cerevisiae; Utp22; ribosomal RNA; ribosomal protein gene; transcription; transcription factor titration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Expression Regulation, Fungal*
  • Organelle Biogenesis
  • Promoter Regions, Genetic
  • Protein Binding
  • RNA Polymerase I / genetics
  • RNA Polymerase I / metabolism
  • RNA, Ribosomal / biosynthesis
  • RNA, Ribosomal / genetics*
  • Ribosomal Proteins / biosynthesis
  • Ribosomal Proteins / genetics*
  • Ribosomal Proteins / metabolism
  • Ribosomes / genetics
  • Ribosomes / metabolism
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism
  • Transcription, Genetic


  • IFH1 protein, S cerevisiae
  • RNA, Ribosomal
  • Ribosomal Proteins
  • Saccharomyces cerevisiae Proteins
  • Trans-Activators
  • Utp22 protein, S cerevisiae
  • RNA Polymerase I