A nutrient-responsive pathway that determines M phase timing through control of B-cyclin mRNA stability

Cell. 2013 May 23;153(5):1080-93. doi: 10.1016/j.cell.2013.04.035.

Abstract

The rate of cell-cycle progression must be tuned in response to nutrient levels to ensure that sufficient materials are synthesized to generate viable daughters. We report that accumulation of the yeast M phase B-cyclin CLB2 mRNA depends on assembly and activation of the heterogeneous nuclear RNA-binding protein (hnRNP) arginine methyltransferase Hmt1, which is promoted by the kinase Dbf2 and countered by the PP2A phosphatase Pph22. Activated Hmt1 methylates hnRNPs, which in turn stabilize CLB2 transcripts. Dbf2 activation of Hmt1 is highly cooperative, producing a sharp increase in CLB2, whereas Pph22 dephosphorylation is graded such that small changes in PP2A activity can cause large shifts in Dbf2-mediated Hmt1 activity. Starvation and rapamycin inhibition of TOR activate Pph22, causing a depletion of CLB2 and delay of M phase. We propose a general model wherein changes to Pph22 activity modulate cyclin mRNA stability to tune cell-cycle progression to environmental conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Division
  • Cell Nucleus / metabolism
  • Cell Physiological Phenomena
  • Cyclin B / genetics*
  • Exoribonucleases / metabolism
  • Molecular Sequence Data
  • Protein Phosphatase 2 / metabolism
  • Protein Serine-Threonine Kinases / metabolism
  • Protein-Arginine N-Methyltransferases / chemistry
  • Protein-Arginine N-Methyltransferases / metabolism
  • RNA Stability*
  • Repressor Proteins / chemistry
  • Repressor Proteins / metabolism
  • Ribonucleases / metabolism
  • Saccharomyces cerevisiae / cytology*
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Sequence Alignment
  • Signal Transduction*

Substances

  • CLB2 protein, S cerevisiae
  • Cyclin B
  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • HMT1 protein, S cerevisiae
  • Protein-Arginine N-Methyltransferases
  • Protein Serine-Threonine Kinases
  • target of rapamycin protein, S cerevisiae
  • CCR4 protein, S cerevisiae
  • Exoribonucleases
  • Ribonucleases
  • XRN1 protein, S cerevisiae
  • Pph22 protein, S cerevisiae
  • Protein Phosphatase 2