Research article Special Issues

Basic, simple and extendable kinetic model of protein synthesis

  • Received: 29 April 2019 Accepted: 18 June 2019 Published: 17 July 2019
  • Protein synthesis is one of the most fundamental biological processes. Despite existence of multiple mathematical models of translation, surprisingly, there is no basic and simple chemical kinetic model of this process, derived directly from the detailed kinetic scheme. One of the reasons for this is that the translation process is characterized by indefinite number of states, because of the structure of the polysome. We bypass this difficulty by applying lumping of multiple states of translated mRNA into few dynamical variables and by introducing a variable describing the pool of translating ribosomes. The simplest model can be solved analytically. The simplest model can be extended, if necessary, to take into account various phenomena such as the limited amount of ribosomal units or regulation of translation by microRNA. The introduced model is more suitable to describe the protein synthesis in eukaryotes but it can be extended to prokaryotes. The model can be used as a building block for more complex models of cellular processes. We demonstrate the utility of the model in two examples. First, we determine the critical parameters of the synthesis of a single protein for the case when the ribosomal units are abundant. Second, we demonstrate intrinsic bi-stability in the dynamics of the ribosomal protein turnover and predict that a minimal number of ribosomes should pre-exists in a living cell to sustain its protein synthesis machinery, even in the absence of proliferation.

    Citation: Alexander N. Gorban, Annick Harel-Bellan, Nadya Morozova, Andrei Zinovyev. Basic, simple and extendable kinetic model of protein synthesis[J]. Mathematical Biosciences and Engineering, 2019, 16(6): 6602-6622. doi: 10.3934/mbe.2019329

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  • Protein synthesis is one of the most fundamental biological processes. Despite existence of multiple mathematical models of translation, surprisingly, there is no basic and simple chemical kinetic model of this process, derived directly from the detailed kinetic scheme. One of the reasons for this is that the translation process is characterized by indefinite number of states, because of the structure of the polysome. We bypass this difficulty by applying lumping of multiple states of translated mRNA into few dynamical variables and by introducing a variable describing the pool of translating ribosomes. The simplest model can be solved analytically. The simplest model can be extended, if necessary, to take into account various phenomena such as the limited amount of ribosomal units or regulation of translation by microRNA. The introduced model is more suitable to describe the protein synthesis in eukaryotes but it can be extended to prokaryotes. The model can be used as a building block for more complex models of cellular processes. We demonstrate the utility of the model in two examples. First, we determine the critical parameters of the synthesis of a single protein for the case when the ribosomal units are abundant. Second, we demonstrate intrinsic bi-stability in the dynamics of the ribosomal protein turnover and predict that a minimal number of ribosomes should pre-exists in a living cell to sustain its protein synthesis machinery, even in the absence of proliferation.


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    [1] F. M. Harold, The vital force?: a study of bioenergetics, W.H. Freeman, 1986.
    [2] J. R. Warner, P. M. Knopf and A. Rich, A multiple ribosomal structure in protein synthesis, Proc. Natl. Acad. Sci. U. S. A., 49 (1963), 122–129.
    [3] A. Rich, J. R. Warner and H. M. Goodman, The Structure and Function of Polyribosomes, Cold Spring Harb. Symp. Quant. Biol., 28 (1963), 269–285.
    [4] C. T. MacDonald, J. H. Gibbs and A. C. Pipkin, Kinetics of biopolymerization on nucleic acid templates, Biopolymers, 6 (1968), 1–25.
    [5] H. F. Lodish, Model for the regulation of mRNA translation applied to haemoglobin synthesis, Nature, 251 (1974), 385–388.
    [6] G. Vassart, J. E. Dumont and F. R. Cantraine, Translational control of protein synthesis: a simulation study, Biochim. Biophys. Acta., 247 (1971), 471–485.
    [7] J. E. Bergmann and H. F. Lodish, A kinetic model of protein synthesis. Application to hemoglobin synthesis and translational control, J. Biol. Chem., 254 (1979), 11927–11937.
    [8] J. Hiernaux, On some stochastic models for protein biosynthesis, Biophys. Chem., 2 (1974), 70–75.
    [9] R. Ordon, Polyribosome dynamics at steady state, J. Theor. Biol., 22 (1969), 515–532.
    [10] R. Heinrich and T. A. Rapoport, Mathematical modelling of translation of mRNA in eucaryotes; steady states, time-dependent processes and application to reticulocytest, J. Theor. Biol., 86 (1980), 279–313.
    [11] H. Zouridis and V. Hatzimanikatis, A Model for Protein Translation: Polysome Self-Organization Leads to Maximum Protein Synthesis Rates, Biophys. J., 92 (2007), 717–730.
    [12] N. Skjndal-Bara and D. R. Morrisb, Dynamic Model of the Process of Protein Synthesis in Eukaryotic Cells, Bull. Math. Biol., 69 (2007), 361–393.
    [13] D. Andreev, M. Arnold, S. Kiniry, et al., TASEP modelling provides a parsimonious explanation for the ability of a single uORF to derepress translation during the integrated stress response, Elife, 7 (2018), e32563.
    [14] L. Ciandrini, I. Stansfield and M. C. Romano, Role of the particle's stepping cycle in an asymmetric exclusion process: A model of mRNA translation, Phys. Rev. E., 81 (2010), 051904.
    [15] P. Bonnin, N. Kern, N. T. Young, et al., Novel mRNA-specific effects of ribosome drop-off on translation rate and polysome profile, PLOS Comput. Biol., 13 (2017), e1005555.
    [16] Y.-B. Zhao and J. Krishnan, mRNA translation and protein synthesis: an analysis of different modelling methodologies and a new PBN based approach, BMC Syst. Biol., 8 (2014), 25.
    [17] C. A. Brackley, D. S. Broomhead, M. C. Romano, et al., A max-plus model of ribosome dynamics during mRNA translation, J. Theor. Biol., 303 (2012), 128–140.
    [18] T. von der Haar, Mathematical and Computational Modelling of Ribosomal Movement and Protein Synthesis: an overview, Comput. Struct. Biotechnol. J., 1 (2012), e201204002.
    [19] T. Nissan and R. O. Y. Parker, Computational analysis of miRNA-mediated repression of translation?: Implications for models of translation initiation inhibition, RNA, 14 (2008), 1480–1491.
    [20] A. Zinovyev, N. Morozova, N. Nonne, et al., Dynamical modeling of microRNA action on the protein translation process, BMC Syst. Biol., 4 (2010), 13.
    [21] M. Jovanovic, M. S. Rooney, P. Mertins, et al., Dynamic profiling of the protein life cycle in response to pathogens, Science, 347 (2015), 1259038.
    [22] A. Battle, Z. Khan, S.H. Wang, etal., Impact ofregulatory variation fromRNA to protein, Science, 347 (2015), 664–667.
    [23] R. Golan-Lavi, C. Giacomelli, G. Fuks, et al., Coordinated Pulses of mRNA and of Protein Translation or Degradation Produce EGF-Induced Protein Bursts, Cell Rep., 18 (2017), 3129–3142.
    [24] K. Z. Coyte, H. Tabuteau, E. A. Gaffney, et al. Reply to Baveye and Darnault: Useful models are simple and extendable, Proc. Natl. Acad. Sci., 114 (2017), E2804–E2805.
    [25] Z. Manojlovic and B. Stefanovic, A novel role of RNA helicase A in regulation of translation of type I collagen mRNAs, RNA, 18 (2012), 321–334.
    [26] U. N. Singh, Polyribosome Dynamics: Size-Distribution as a Function of Attachment, Translocation and Release of Ribosomes, J. Theor. Biol. 179 (1996), 147–159.
    [27] N. Morozova, A. Zinovyev, N. Nonne, et al., Kinetic signatures of microRNA modes of action, RNA, 18 (2012), 1635–1655.
    [28] L. Cantini, M. Caselle, A. Forget, et al., A review of computational approaches detecting microRNAs involved in cancer, Front. Biosci. - Landmark, 22 (2017), 1774–1791.
    [29] L. Cantini, G. Bertoli, C. Cava, et al., Identification of microRNA clusters cooperatively acting on epithelial to mesenchymal transition in triple negative breast cancer, Nucleic Acids Res., 47 (2019), 2209–2215.
    [30] A. Zinovyev, N. Morozova, A. N. Gorban, et al., In MiRNA Cancer Regulation: Advanced Concepts, Bioinformatics and Systems Biology Tools (ed. Schmitz U, Wolkenhauer O, Vera J), Springer, 2013, 189–224..
    [31] N. T. Ingolia, S. Ghaemmaghami, J. R. S. Newman, et al., Genome-Wide Analysis in Vivo of Translation with Nucleotide Resolution Using Ribosome Profiling, Science, 324 (2009), 218–223.
    [32] I. G. Cannell, Y. W. Kong and M. Bushell, How do microRNAs regulate gene expression?, Biochem. Soc. Trans., 36 (2008), 1224–1231.
    [33] R. Milo and R. Phillips, Cell biology by the numbers, Garland Science, Taylor & Francis Group, New-York, 2016.
    [34] A. N. Gorban, O. Radulescu and A. Y. Zinovyev, Asymptotology of chemical reaction networks, Chem. Eng. Sci., 65 (2010), 2310–2324.
    [35] J. Zhao, B. Qin, R. Nikolay, et al., Translatomics: The Global View of Translation, Int. J. Mol. Sci., 20 (2019), E212.
    [36] D. Andreev, P. O'Connor, G. Loughran, et al., Insights into the mechanisms of eukaryotic translation gained with ribosome profiling, Nucleic Acids Res., 45 (2017), 513–526.
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