Cdk1 gates cell cycle-dependent tRNA synthesis by regulating RNA polymerase III activity

Nucleic Acids Res. 2018 Dec 14;46(22):11698-11711. doi: 10.1093/nar/gky846.


tRNA genes are transcribed by RNA polymerase III (RNAPIII). During recent years it has become clear that RNAPIII activity is strictly regulated by the cell in response to environmental cues and the homeostatic status of the cell. However, the molecular mechanisms that control RNAPIII activity to regulate the amplitude of tDNA transcription in normally cycling cells are not well understood. Here, we show that tRNA levels fluctuate during the cell cycle and reveal an underlying molecular mechanism. The cyclin Clb5 recruits the cyclin dependent kinase Cdk1 to tRNA genes to boost tDNA transcription during late S phase. At tDNA genes, Cdk1 promotes the recruitment of TFIIIC, stimulates the interaction between TFIIIB and TFIIIC, and increases the dynamics of RNA polymerase III in vivo. Furthermore, we identified Bdp1 as a putative Cdk1 substrate in this process. Preventing Bdp1 phosphorylation prevented cell cycle-dependent recruitment of TFIIIC and abolished the cell cycle-dependent increase in tDNA transcription. Our findings demonstrate that under optimal growth conditions Cdk1 gates tRNA synthesis in S phase by regulating the RNAPIII machinery, revealing a direct link between the cell cycle and RNAPIII activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CDC2 Protein Kinase / genetics*
  • CDC2 Protein Kinase / metabolism
  • CDC28 Protein Kinase, S cerevisiae / genetics*
  • CDC28 Protein Kinase, S cerevisiae / metabolism
  • Cell Cycle / genetics*
  • Cyclin B / genetics
  • Cyclin B / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Fungal
  • Phosphorylation
  • Protein Binding
  • RNA Polymerase III / genetics*
  • RNA Polymerase III / metabolism
  • RNA, Transfer / genetics*
  • RNA, Transfer / metabolism
  • S Phase / genetics
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Transcription Factor TFIIIB / genetics
  • Transcription Factor TFIIIB / metabolism
  • Transcription Factors, TFIII / genetics
  • Transcription Factors, TFIII / metabolism


  • Bdp1 protein, S cerevisiae
  • CLB5 protein, S cerevisiae
  • Cyclin B
  • Saccharomyces cerevisiae Proteins
  • Transcription Factor TFIIIB
  • Transcription Factors, TFIII
  • transcription factor TFIIIC
  • RNA, Transfer
  • CDC2 Protein Kinase
  • CDC28 Protein Kinase, S cerevisiae
  • RNA Polymerase III