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A low number of SIC1 mRNA molecules ensures a low noise level in cell cycle progression of budding yeast

Barberis, Matteo, Beck, C., Amoussouvi, A., Schreiber, G., Diener, C., Herrmann, A. and Klipp, E. (2011) A low number of SIC1 mRNA molecules ensures a low noise level in cell cycle progression of budding yeast Molecular BioSystems, 7 (10). pp. 2804-2812.

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The budding yeast genome comprises roughly 6000 genes generating a number of about 10000 mRNA copies, which gives a general estimation of 1-2 mRNA copies generated per gene. What does this observation implicate for cellular processes and their regulation? Whether the number of mRNA molecules produced is important for setting the amount of proteins implicated in a particular function is at present unknown. In this context, we studied cell cycle control as one of the highly fine tuned processes that guarantee the precise timing of events essential for cell growth. Here, we developed a stochastic model that addresses the effect of varying the mRNA amount of Sic1, inhibitor of the Cdk1-Clb5 kinase activity, and the resulting noise on Sic1/Clb5 balance at the G1/S transition. We considered a range of SIC1 transcripts number according to our experimental data derived from the MS2 mRNA tagging system. Computational simulation revealed that an increased amount of SIC1 mRNAs lead to an amplified dispersion of Sic1 protein levels, suggesting mRNA control being critical to set timing of Sic1 downregulation and, therefore, S phase onset. Moreover, Sic1/Clb5 balance is strongly influenced by Clb5 production in both daughter and mother cells in order to maintain the characteristic time of S phase entry overall the population. Furthermore, CLB5 mRNA molecules calculated to reproduce temporal dynamics of Sic1 and Clb5 for daughter and mother cells agree with recent data obtained from more complex networks. Thus, the results presented here provide novel insights into the influence that the mRNA amount and, indirectly, the transcription process exploit on cell cycle progression. © 2011 The Royal Society of Chemistry.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
Beck, C.
Amoussouvi, A.
Schreiber, G.
Diener, C.
Herrmann, A.
Klipp, E.
Date : 30 June 2011
DOI : 10.1039/c1mb05073g
Depositing User : Clive Harris
Date Deposited : 16 Apr 2019 10:06
Last Modified : 16 Apr 2019 10:06

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