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Layers of regulation of cell-cycle gene expression in the budding yeast Saccharomyces cerevisiae.

Publication ,  Journal Article
Kelliher, CM; Foster, MW; Motta, FC; Deckard, A; Soderblom, EJ; Moseley, MA; Haase, SB
Published in: Mol Biol Cell
November 1, 2018

In the budding yeast Saccharomyces cerevisiae, transcription factors (TFs) regulate the periodic expression of many genes during the cell cycle, including gene products required for progression through cell-cycle events. Experimental evidence coupled with quantitative models suggests that a network of interconnected TFs is capable of regulating periodic genes over the cell cycle. Importantly, these dynamical models were built on transcriptomics data and assumed that TF protein levels and activity are directly correlated with mRNA abundance. To ask whether TF transcripts match protein expression levels as cells progress through the cell cycle, we applied a multiplexed targeted mass spectrometry approach (parallel reaction monitoring) to synchronized populations of cells. We found that protein expression of many TFs and cell-cycle regulators closely followed their respective mRNA transcript dynamics in cycling wild-type cells. Discordant mRNA/protein expression dynamics was also observed for a subset of cell-cycle TFs and for proteins targeted for degradation by E3 ubiquitin ligase complexes such as SCF (Skp1/Cul1/F-box) and APC/C (anaphase-promoting complex/cyclosome). We further profiled mutant cells lacking B-type cyclin/CDK activity ( clb1-6) where oscillations in ubiquitin ligase activity, cyclin/CDKs, and cell-cycle progression are halted. We found that a number of proteins were no longer periodically degraded in clb1-6 mutants compared with wild type, highlighting the importance of posttranscriptional regulation. Finally, the TF complexes responsible for activating G1/S transcription (SBF and MBF) were more constitutively expressed at the protein level than at periodic mRNA expression levels in both wild-type and mutant cells. This comprehensive investigation of cell-cycle regulators reveals that multiple layers of regulation (transcription, protein stability, and proteasome targeting) affect protein expression dynamics during the cell cycle.

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Published In

Mol Biol Cell

DOI

EISSN

1939-4586

Publication Date

November 1, 2018

Volume

29

Issue

22

Start / End Page

2644 / 2655

Location

United States

Related Subject Headings

  • Transcriptome
  • Transcription Factors
  • Saccharomyces cerevisiae Proteins
  • Saccharomyces cerevisiae
  • Reproducibility of Results
  • Proteome
  • Mutation
  • Models, Biological
  • Mass Spectrometry
  • Gene Expression Regulation, Fungal
 

Citation

APA
Chicago
ICMJE
MLA
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Kelliher, C. M., Foster, M. W., Motta, F. C., Deckard, A., Soderblom, E. J., Moseley, M. A., & Haase, S. B. (2018). Layers of regulation of cell-cycle gene expression in the budding yeast Saccharomyces cerevisiae. Mol Biol Cell, 29(22), 2644–2655. https://doi.org/10.1091/mbc.E18-04-0255
Kelliher, Christina M., Matthew W. Foster, Francis C. Motta, Anastasia Deckard, Erik J. Soderblom, M Arthur Moseley, and Steven B. Haase. “Layers of regulation of cell-cycle gene expression in the budding yeast Saccharomyces cerevisiae.Mol Biol Cell 29, no. 22 (November 1, 2018): 2644–55. https://doi.org/10.1091/mbc.E18-04-0255.
Kelliher CM, Foster MW, Motta FC, Deckard A, Soderblom EJ, Moseley MA, et al. Layers of regulation of cell-cycle gene expression in the budding yeast Saccharomyces cerevisiae. Mol Biol Cell. 2018 Nov 1;29(22):2644–55.
Kelliher, Christina M., et al. “Layers of regulation of cell-cycle gene expression in the budding yeast Saccharomyces cerevisiae.Mol Biol Cell, vol. 29, no. 22, Nov. 2018, pp. 2644–55. Pubmed, doi:10.1091/mbc.E18-04-0255.
Kelliher CM, Foster MW, Motta FC, Deckard A, Soderblom EJ, Moseley MA, Haase SB. Layers of regulation of cell-cycle gene expression in the budding yeast Saccharomyces cerevisiae. Mol Biol Cell. 2018 Nov 1;29(22):2644–2655.

Published In

Mol Biol Cell

DOI

EISSN

1939-4586

Publication Date

November 1, 2018

Volume

29

Issue

22

Start / End Page

2644 / 2655

Location

United States

Related Subject Headings

  • Transcriptome
  • Transcription Factors
  • Saccharomyces cerevisiae Proteins
  • Saccharomyces cerevisiae
  • Reproducibility of Results
  • Proteome
  • Mutation
  • Models, Biological
  • Mass Spectrometry
  • Gene Expression Regulation, Fungal