The importance of controlling mRNA turnover during cell proliferation
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Microbial gene expression depends not only on specific regulatory mechanisms, but also on cellular growth because important global parameters, such as abundance of mRNAs and ribosomes, could be growth rate dependent. Understanding these global effects is necessary to quantitatively judge gene regulation. In the last few years, transcriptomic works in budding yeast have shown that a large fraction of its genes is coordinately regulated with growth rate. As mRNA levels depend simultaneously on synthesis and degradation rates, those studies were unable to discriminate the respective roles of both arms of the equilibrium process. We recently analyzed 80 different genomic experiments and found a positive and parallel correlation between both RNA polymerase II transcription and mRNA degradation with growth rates. Thus, the total mRNA concentration remains roughly constant. Some gene groups, however, regulate their mRNA concentration by uncoupling mRNA stability from the transcription rate. Ribosome-related genes modulate their transcription rates to increase mRNA levels under fast growth. In contrast, mitochondria-related and stress-induced genes lower mRNA levels by reducing mRNA stability or the transcription rate, respectively. We critically review here these results and analyze them in relation to their possible extrapolation to other organisms and in relation to the new questions they open.
KeywordsGrowth rate Gene expression mRNA turnover Yeast Transcription mRNA half-life
We wish to thank all the members of the Valencia and Seville laboratories for their help.
This work has been supported by the Spanish MiNECO and European Union funds (FEDER) to J.E.P-O. [BFU2013-48643-C3-3-P], and to S.C. [BFU2013-48643-C3-1-P], by the Regional Valencian Government [GVPROMETEO II 2015/006] to J.E.P-O, and by the Regional Andalusian Government [P12-BIO1938MO] to S.C. L.D-R. is a recipient of an FPI fellowship from MiNECO.
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Conflict of interest
The authors declare that they have no conflict of interest.
- Bremer H, Dennis P (1996) Modulation of chemical composition and other parameters of the cell by growth rate in Escherichia coli and Salmonella. In: Neidhardt F (ed) 2nd edn. ASM press, Washington, pp 1553–1569Google Scholar
- Castrillo JI, Zeef LA, Hoyle DC, Zhang N, Hayes A, Gardner DC, Cornell MJ, Petty J, Hakes L, Wardleworth L, Rash B, Brown M, Dunn WB, Broadhurst D, O’Donoghue K, Hester SS, Dunkley TP, Hart SR, Swainston N, Li P, Gaskell SJ, Paton NW, Lilley KS, Kell DB, Oliver SG (2007) Growth control of the eukaryote cell: a systems biology study in yeast. J Biol 6:4CrossRefPubMedPubMedCentralGoogle Scholar
- García-Martínez J, Delgado-Ramos L, Ayala G, Pelechano V, Medina DA, Carrasco F, González R, AndrésLeón E, Steinmetz L, Warringer J, Chávez S, Pérez-Ortín JE (2016) The cellular growth rate controls overall mRNA turnover, and modulates either transcription or degradation rates of particular gene regulons. Nucleic Acids Res (in press)Google Scholar
- Gómez-Herreros F, Rodríguez-Galán O, Morillo-Huesca M, Maya D, Arista-Romero M, de la Cruz J, Chávez S, Muñoz-Centeno MC (2013) Balanced production of ribosome components is required for proper G1/S transition in Saccharomyces cerevisiae. J Biol Chem 288:31689–31700CrossRefPubMedPubMedCentralGoogle Scholar
- Gresham D, Athanasiadou R, Neymotin B et al (2015) Global tuning of gene expression with cell growth rate. Yeast 32(Supl 1):S37Google Scholar