Cooperative Action of Cdk1/cyclin B and SIRT1 Is Required for Mitotic Repression of rRNA Synthesis

PLoS Genet. 2015 May 29;11(5):e1005246. doi: 10.1371/journal.pgen.1005246. eCollection 2015 May.

Abstract

Mitotic repression of rRNA synthesis requires inactivation of the RNA polymerase I (Pol I)-specific transcription factor SL1 by Cdk1/cyclin B-dependent phosphorylation of TAF(I)110 (TBP-associated factor 110) at a single threonine residue (T852). Upon exit from mitosis, T852 is dephosphorylated by Cdc14B, which is sequestered in nucleoli during interphase and is activated upon release from nucleoli at prometaphase. Mitotic repression of Pol I transcription correlates with transient nucleolar enrichment of the NAD(+)-dependent deacetylase SIRT1, which deacetylates another subunit of SL1, TAFI68. Hypoacetylation of TAFI68 destabilizes SL1 binding to the rDNA promoter, thereby impairing transcription complex assembly. Inhibition of SIRT1 activity alleviates mitotic repression of Pol I transcription if phosphorylation of TAF(I)110 is prevented. The results demonstrate that reversible phosphorylation of TAF(I)110 and acetylation of TAFI68 are key modifications that regulate SL1 activity and mediate fluctuations of pre-rRNA synthesis during cell cycle progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • CDC2 Protein Kinase
  • Cell Nucleolus / genetics
  • Cyclin B / genetics
  • Cyclin B / metabolism
  • Cyclin-Dependent Kinases / genetics
  • Cyclin-Dependent Kinases / metabolism
  • Dual-Specificity Phosphatases / genetics*
  • Dual-Specificity Phosphatases / metabolism
  • HeLa Cells
  • Histone Chaperones / genetics
  • Humans
  • Mitosis
  • Phosphorylation
  • Pol1 Transcription Initiation Complex Proteins / genetics*
  • Pol1 Transcription Initiation Complex Proteins / metabolism
  • RNA Polymerase I / genetics
  • RNA, Ribosomal / biosynthesis
  • RNA, Ribosomal / genetics
  • Sirtuin 1 / genetics*
  • Sirtuin 1 / metabolism
  • Transcription Factor TFIID / genetics*
  • Transcription Factor TFIID / metabolism
  • Transcription Factors / genetics
  • Transcription, Genetic*

Substances

  • Cyclin B
  • Histone Chaperones
  • Pol1 Transcription Initiation Complex Proteins
  • RNA, Ribosomal
  • SET protein, human
  • Transcription Factor TFIID
  • Transcription Factors
  • transcription initiation factor TIF-IB
  • CDC2 Protein Kinase
  • CDK1 protein, human
  • Cyclin-Dependent Kinases
  • RNA Polymerase I
  • CDC14B protein, human
  • Dual-Specificity Phosphatases
  • SIRT1 protein, human
  • Sirtuin 1

Grant support

This work was supported by the Deutsche Forschungsgemeinschaft: Grant number: GR475/22-1 (to IG), and grant number: SFB 1036 (to IG and RV). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.