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Current Genetics

, Volume 62, Issue 4, pp 701–710 | Cite as

The importance of controlling mRNA turnover during cell proliferation

  • Sebastián ChávezEmail author
  • José García-Martínez
  • Lidia Delgado-Ramos
  • José E. Pérez-OrtínEmail author
Review

Abstract

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.

Keywords

Growth rate Gene expression mRNA turnover Yeast Transcription mRNA half-life 

Notes

Acknowledgments

We wish to thank all the members of the Valencia and Seville laboratories for their help.

Funding

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.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Airoldi EM, Huttenhower C, Gresham D, Lu C, Caudy AA, Dunham MJ, Broach JR, Botstein D, Troyanskaya OG (2009) Predicting cellular growth from gene expression signatures. PLoS Comput Biol 5:e1000257CrossRefPubMedPubMedCentralGoogle Scholar
  2. Basehoar AD, Zanton SJ, Pugh BF (2004) Identification and distinct regulation of yeast TATA box-containing genes. Cell 116:699–709CrossRefPubMedGoogle Scholar
  3. Bosdriesz E, Molenaar D, Teusink B, Bruggeman FJ (2015) How fast-growing bacteria robustly tune their ribosome concentration to approximate growth-rate maximization. FEBS J 282:2029–2044CrossRefPubMedPubMedCentralGoogle Scholar
  4. Brauer MJ, Huttenhower C, Airoldi EM, Rosenstein R, Matese JC, Gresham D, Boer VM, Troyanskaya OG, Botstein D (2008) Coordination of growth rate, cell cycle, stress response, and metabolic activity in yeast. Mol Biol Cell 19:352–367CrossRefPubMedPubMedCentralGoogle Scholar
  5. 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
  6. Canadell D, García-Martínez J, Alepuz P, Pérez-Ortín JE, Ariño J (2015) Impact of high pH stress on yeast gene expression: a comprehensive analysis of mRNA turnover during stress responses. Biochim Biophys Acta 1849:653–664CrossRefPubMedGoogle Scholar
  7. 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
  8. Csárdi G, Franks A, Choi DS, Airoldi EM, Drummond DA (2015) Accounting for experimental noise reveals that mRNA levels, amplified by post-transcriptional processes, largely determine steady-state protein levels in yeast. PLoS Genet 11:e1005206CrossRefPubMedPubMedCentralGoogle Scholar
  9. Eser P, Demel C, Maier KC, Schwalb B, Pirkl N, Martin DE, Cramer P, Tresch A (2014) Periodic mRNA synthesis and degradation co-operate during cell cycle gene expression. Mol Syst Biol 10:717CrossRefPubMedPubMedCentralGoogle Scholar
  10. Ferrezuelo F, Colomina N, Palmisano A, Garí E, Gallego C, Csikász-Nagy A, Aldea M (2012) The critical size is set at a single-cell level by growth rate to attain homeostasis and adaptation. Nat Commun 3:1012CrossRefPubMedGoogle Scholar
  11. García-Martínez J, Aranda A, Pérez-Ortín JE (2004) Genomic run-on evaluates transcription rates for all yeast genes and identifies gene regulatory mechanisms. Mol Cell 15:303–313CrossRefPubMedGoogle Scholar
  12. García-Martínez J, González-Candelas F, Pérez-Ortín JE (2007) Common gene expression strategies revealed by genome-wide analysis in yeast. Genome Biol 8:R222CrossRefPubMedPubMedCentralGoogle Scholar
  13. 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
  14. Gasch AP, Spellman PT, Kao CM, Carmel-Harel O, Eisen MB, Storz G, Botstein D, Brown PO (2000) Genomic expression programs in the response of yeast cells to environmental changes. Mol Biol Cell 11:4241–4257CrossRefPubMedPubMedCentralGoogle Scholar
  15. Goler-Baron V, Selitrennik M, Barkai O, Haimovich G, Lotan R, Choder M (2008) Transcription in the nucleus and mRNA decay in the cytoplasm are coupled processes. Genes Dev 22:2022–2027CrossRefPubMedPubMedCentralGoogle Scholar
  16. 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
  17. Gresham D, Athanasiadou R, Neymotin B et al (2015) Global tuning of gene expression with cell growth rate. Yeast 32(Supl 1):S37Google Scholar
  18. Hagman A, Piškur J (2015) A study on the fundamental mechanism and the evolutionary driving forces behind aerobic fermentation in yeast. PLoS ONE 10:e0116942CrossRefPubMedPubMedCentralGoogle Scholar
  19. Haimovich G, Medina DA, Causse SZ, Garber M, Millán-Zambrano G, Barkai O, Chávez S, Pérez-Ortín JE, Darzacq X, Choder M (2013) Gene expression is circular: factors for mRNA degradation also foster mRNA synthesis. Cell 153:1000–1011CrossRefPubMedGoogle Scholar
  20. Harel-Sharvit L, Eldad N, Haimovich G, Barkai O, Duek L, Choder M (2010) RNA polymerase II subunits link transcription and mRNA decay to translation. Cell 143:552–563CrossRefPubMedGoogle Scholar
  21. Ho YH, Gasch AP (2015) Exploiting the yeast stress-activated signaling network to inform on stress biology and disease signaling. Curr Genet 61(4):503–511CrossRefPubMedPubMedCentralGoogle Scholar
  22. Huh D, Paulsson J (2011) Random partitioning of molecules at cell division. Proc Natl Acad Sci USA 108:15004–15009CrossRefPubMedPubMedCentralGoogle Scholar
  23. Huisinga KL, Pugh BF (2004) A genome-wide housekeeping role for TFIID and a highly regulated stress-related role for SAGA in Saccharomyces cerevisiae. Mol Cell 13:573–585CrossRefPubMedGoogle Scholar
  24. Ihmels J, Bergmann S, Gerami-Nejad M, Yanai I, McClellan M, Berman J, Barkai N (2005a) Rewiring of the yeast transcriptional network through the evolution of motif usage. Science 309:938–940CrossRefPubMedGoogle Scholar
  25. Ihmels J, Bergmann S, Berman J, Barkai N (2005b) Comparative gene expression analysis by differential clustering approach: application to the Candida albicans transcription program. PLoS Genet 1:e39CrossRefPubMedPubMedCentralGoogle Scholar
  26. Jordán-Pla A, Gupta I, de Miguel-Jiménez L, Steinmetz LM, Chávez S, Pelechano V, Pérez-Ortín JE (2015) Chromatin-dependent regulation of RNA polymerases II and III activity throughout the transcription cycle. Nucleic Acids Res 43:787–802CrossRefPubMedGoogle Scholar
  27. Jorgensen P, Rupes I, Sharom JR, Schneper L, Broach JR, Tyers M (2004) A dynamic transcriptional network communicates growth potential to ribosome synthesis and critical cell size. Genes Dev 18:2491–2505CrossRefPubMedPubMedCentralGoogle Scholar
  28. Kaczanowska M, Rydén-Aulin M (2007) Ribosome biogenesis and the translation process in Escherichia coli. Microbiol Mol Biol Rev 71:477–494CrossRefPubMedPubMedCentralGoogle Scholar
  29. Kafri M, Metzl-Raz E, Jona G, Barkai N (2016) The cost of protein production. Cell Rep 14:22–31CrossRefPubMedGoogle Scholar
  30. Klevecz RR, Bolen J, Forrest G, Murray DB (2004) A genome-wide oscillation in transcription gates DNA replication and cell cycle. Proc Natl Acad Sci USA 101:1200–1205CrossRefPubMedPubMedCentralGoogle Scholar
  31. Klumpp S, Zhang Z, Hwa T (2009) Growth rate-dependent global effects on gene expression in bacteria. Cell 139:1366–1375CrossRefPubMedPubMedCentralGoogle Scholar
  32. Kruk JA, Dutta A, Fu J, Gilmour DS, Reese JC (2011) The multifunctional Ccr4-Not complex directly promotes transcription elongation. Genes Dev 25:581–593CrossRefPubMedPubMedCentralGoogle Scholar
  33. Kubik S, Bruzzone MJ, Jacquet P, Falcone JL, Rougemont J, Shore D (2015) Nucleosome stability distinguishes two different promoter types at all protein-coding genes in yeast. Mol Cell 60:422–434CrossRefPubMedGoogle Scholar
  34. Lemons JM, Feng XJ, Bennett BD, Legesse-Miller A, Johnson EL, Raitman I, Pollina EA, Rabitz HA, Rabinowitz JD, Coller HA (2010) Quiescent fibroblasts exhibit high metabolic activity. PLoS Biol 8:e1000514CrossRefPubMedPubMedCentralGoogle Scholar
  35. Levy S, Barkai N (2009) Coordination of gene expression with growth rate: a feedback or a feed-forward strategy? FEBS Lett 583:3974–3978CrossRefPubMedGoogle Scholar
  36. Levy S, Ihmels J, Carmi M, Weinberger A, Friedlander G, Barkai N (2007) Strategy of transcription regulation in the budding yeast. PLoS ONE 2:e250CrossRefPubMedPubMedCentralGoogle Scholar
  37. Li JJ, Biggin MD (2015) Gene expression. Statistics requantitates the central dogma. Science 347:1066–1067PubMedGoogle Scholar
  38. Lu C, Brauer MJ, Botstein D (2009) Slow growth induces heat-shock resistance in normal and respiratory-deficient yeast. Mol Biol Cell 20:891–903CrossRefPubMedPubMedCentralGoogle Scholar
  39. Miguel A, Montón F, Li T, Gómez-Herreros F, Chávez S, Alepuz P, Pérez-Ortín JE (2013) External conditions inversely change the RNA polymerase II elongation rate and density in yeast. Biochim Biophys Acta 1829:1248–1255CrossRefPubMedGoogle Scholar
  40. Miller MA, Russo J, Fischer AD, Lopez Leban FA, Olivas WM (2014) Carbon source-dependent alteration of Puf3p activity mediates rapid changes in the stabilities of mRNAs involved in mitochondrial function. Nucleic Acids Res 42:3954–3970CrossRefPubMedGoogle Scholar
  41. Molin C, Jauhiainen A, Warringer J, Nerman O, Sunnerhagen P (2009) mRNA stability changes precede changes in steady-state mRNA amounts during hyperosmotic stress. RNA 15:600–614CrossRefPubMedPubMedCentralGoogle Scholar
  42. Molina-Navarro MM, Castells-Roca L, Belli G, Garcia-Martinez J, Marin-Navarro J, Moreno J, Perez-Ortin JE, Herrero E (2008) Comprehensive transcriptional analysis of the oxidative response in yeast. J Biol Chem 283:17908–17918CrossRefPubMedGoogle Scholar
  43. Newman J, Ghaemmaghami S, Ihmels J, Breslow D, Noble M, DeRisi J, Weissman J (2006) Single-cell proteomic analysis of S. cerevisiae reveals the architecture of biological noise. Nature 441:840–846CrossRefPubMedGoogle Scholar
  44. O’Duibhir E, Lijnzaad P, Benschop JJ, Lenstra TL, van Leenen D, Groot Koerkamp MJ, Margaritis T, Brok MO, Kemmeren P, Holstege FC (2014) Cell cycle population effects in perturbation studies. Mol Syst Biol 10:732CrossRefPubMedPubMedCentralGoogle Scholar
  45. Olivas W, Parker R (2000) The Puf3 protein is a transcript-specific regulator of mRNA degradation in yeast. EMBO J 19:6602–6611CrossRefPubMedPubMedCentralGoogle Scholar
  46. Paulsson J (2004) Summing up the noise in gene networks. Nature 427:415–418CrossRefPubMedGoogle Scholar
  47. Pedersen S, Bloch PL, Reeh S, Neidhardt FC (1978) Patterns of protein synthesis in E. coli: a catalog of the amount of 140 individual proteins at different growth rates. Cell 14:179–190CrossRefPubMedGoogle Scholar
  48. Pelechano V, Jimeno-González S, Rodríguez-Gil A, García-Martínez J, Pérez-Ortín JE, Chávez S (2009) Regulon-specific control of transcription elongation across the yeast genome. PLoS Genet 5:e1000614CrossRefPubMedPubMedCentralGoogle Scholar
  49. Peng X, Karuturi RK, Miller LD, Lin K, Jia Y, Kondu P, Wang L, Wong LS, Liu ET, Balasubramanian MK, Liu J (2005) Identification of cell cycle-regulated genes in fission yeast. Mol Biol Cell 16:1026–1042CrossRefPubMedPubMedCentralGoogle Scholar
  50. Pérez-Ortín JE, Alepuz PM, Moreno J (2007) Genomics and gene transcription kinetics in yeast. Trends Genet 23:250–257CrossRefPubMedGoogle Scholar
  51. Pérez-Ortín JE, Jordán-Pla A, Pelechano V (2011) A genomic view of mRNA turnover in yeast. C R Biol 334:647–654CrossRefPubMedGoogle Scholar
  52. Pérez-Ortín JE, Alepuz P, Chávez S, Choder M (2013) Eukaryotic mRNA decay: methodologies, pathways, and links to other stages of gene expression. J Mol Biol 425:3750–3775CrossRefPubMedGoogle Scholar
  53. Ramaswami M, Taylor JP, Parker R (2013) Altered ribostasis: RNA-protein granules in degenerative disorders. Cell 154:727–736CrossRefPubMedGoogle Scholar
  54. Rhee HS, Pugh BF (2012) Genome-wide structure and organization of eukaryotic pre-initiation complexes. Nature 483:295–301CrossRefPubMedPubMedCentralGoogle Scholar
  55. Romero-Santacreu L, Moreno J, Perez-Ortin JE, Alepuz P (2009) Specific and global regulation of mRNA stability during osmotic stress in Saccharomyces cerevisiae. RNA 2009(15):1110–1120CrossRefGoogle Scholar
  56. Rustici G, Mata J, Kivinen K, Lió P, Penkett CJ, Burns G, Hayles J, Brazma A, Nurse P, Bähler J (2004) Periodic gene expression program of the fission yeast cell cycle. Nat Genet 3:809–817CrossRefGoogle Scholar
  57. Schell JC, Olson KA, Jiang L, Hawkins AJ, Van Vranken JG, Xie J, Egnatchik RA, Earl EG, DeBerardinis RJ, Rutter J (2014) A role for the mitochondrial pyruvate carrier as a repressor of the Warburg effect and colon cancer cell growth. Mol Cell 56:400–413CrossRefPubMedPubMedCentralGoogle Scholar
  58. Schuster S, Boley D, Möller P, Stark H, Kaleta C (2015) Mathematical models for explaining the Warburg effect: a review focussed on ATP and biomass production. Biochem Soc Trans 43:1187–1194CrossRefPubMedGoogle Scholar
  59. Scott M, Gunderson CW, Mateescu EM, Zhang Z, Hwa T (2010) Interdependence of cell growth and gene expression: origins and consequences. Science 330:1099–1102CrossRefPubMedGoogle Scholar
  60. Scott M, Klumpp S, Mateescu EM, Hwa T (2014) Emergence of robust growth laws from optimal regulation of ribosome synthesis. Mol Syst Biol 10:747CrossRefPubMedPubMedCentralGoogle Scholar
  61. Shahrezaei V, Marguerat S (2015) Connecting growth with gene expression: of noise and numbers. Curr Opin Microbiol 25:127–135CrossRefPubMedGoogle Scholar
  62. Shalem O, Groisman B, Choder M, Dahan O, Pilpel Y (2011) Transcriptome kinetics is governed by a genome-wide coupling of mRNA production and degradation: a role for RNA Pol II. PLoS Genet 7:e1002273CrossRefPubMedPubMedCentralGoogle Scholar
  63. Slavov N, Botstein D (2011) Coupling among growth rate response, metabolic cycle, and cell division cycle in yeast. Mol Biol Cell 22:1997–2009CrossRefPubMedPubMedCentralGoogle Scholar
  64. Slavov N, Botstein D (2013) Decoupling nutrient signaling from growth rate causes aerobic glycolysis and deregulation of cell size and gene expression. Mol Biol Cell 24:157–168CrossRefPubMedPubMedCentralGoogle Scholar
  65. Slavov N, Macinskas J, Caudy A, Botstein D (2011) Metabolic cycling without cell division cycling in respiring yeast. Proc Natl Acad Sci USA 108:19090–19095CrossRefPubMedPubMedCentralGoogle Scholar
  66. Slavov N, Airoldi EM, van Oudenaarden A, Botstein D (2012) A conserved cell growth cycle can account for the environmental stress responses of divergent eukaryotes. Mol Biol Cell 23:1986–1997CrossRefPubMedPubMedCentralGoogle Scholar
  67. Solé C, Nadal-Ribelles M, de Nadal E, Posas F (2015) A novel role for lncRNAs in cell cycle control during stress adaptation. Curr Genet 61:299–308CrossRefPubMedGoogle Scholar
  68. Sun M, Schwalb B, Pirkl N, Maier KC, Schenk A, Failmezger H, Tresch A, Cramer P (2013) Global analysis of eukaryotic mRNA degradation reveals Xrn1-dependent buffering of transcript levels. Mol Cell 52:52–62CrossRefPubMedGoogle Scholar
  69. Tu BP, Kudlicki A, Rowicka M, McKnight SL (2005) Logic of the yeast metabolic cycle: temporal compartmentalization of cellular processes. Science 310:1152–1158CrossRefPubMedGoogle Scholar
  70. van Dijk D, Dhar R, Missarova AM, Espinar L, Blevins WR, Lehner B, Carey LB (2015) Slow-growing cells within isogenic populations have increased RNA polymerase error rates and DNA damage. Nat Commun 6:7972CrossRefPubMedPubMedCentralGoogle Scholar
  71. Warner JR (1999) The economics of ribosome biosynthesis in yeast. Trends Biochem Sci 24:437–440CrossRefPubMedGoogle Scholar
  72. Whiteway M, Tebung WA, Choudhury BI, Rodríguez-Ortiz R (2015) Metabolic regulation in model ascomycetes–adjusting similar genomes to different lifestyles. Trends Genet 31:445–453CrossRefPubMedGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Instituto de Biomedicina de Sevilla (IBiS), Hospital Virgen del Rocío-CSIC-Universidad de SevillaSevilleSpain
  2. 2.Departamento de GenéticaUniversidad de SevillaSevilleSpain
  3. 3.Departamento de GenéticaUniversitat de ValènciaBurjassotSpain
  4. 4.Departamento de Bioquímica y Biología MolecularUniversitat de ValènciaBurjassotSpain
  5. 5.ERI BiotecmedUniversitat de ValènciaBurjassotSpain

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