Abstract
Protein synthesis is the final step of gene expression in all cells. In order to understand the regulation of this process, it is important to have an accurate model that incorporates the regulatory steps. The model presented in this paper is composed of set of differential equations which describe the dynamics of the initiation process and its control, as well as peptide elongation, starting with the amino acids available for peptide creation. A novel approach for modeling the elongation process permits useful prediction of protein production and consumption of energy and amino acids, as well as ribosome loading rate and ribosome spacing on the mRNA.
Similar content being viewed by others
References
Arava, Y., Wang, Y., Storey, J., Liu, C., Brown, P., Herschlag, D., 2003. Genome-wide analysis of mRNA translation profiles in saccharomyces cerevisiae. Proc. Natl. Acad. Sci. U.S.A. 100(7), 3889–3894.
Drew, D.A., 2001. A mathematical model for prokaryotic protein synthesis. Bull. Math. Biol. (63), 329–351.
Gingras, A.C., Raught, B., Sonenberg, N., 1999. eIF4 initiation factors: Effectors of mRNA recruitment to ribosomes and regulators of translation. Annu. Rev. Biochem. 68, 913–963.
Hinnebusch, A.G., 2000. Mechanism and regulation of initiator methionyl-tRNA binding to ribosomes. In: Sonenberg, N., Hershey, J., Mathews, M.B. (Eds.), Translational Control of Gene Expression. Cold Spring Harbor Laboratory Press, New York, pp. 185–243 (Chapter 5).
Hinnebusch, A.G., 2004. Study of translational control in eukaryotic gene expression using yeast. Ann. N.Y. Acad. Sci. 1038, 60–74.
Holcik, M., Sonenberg, N., 2005. Translational control in stress and apoptosis. Nat. Rev. Mol. Cell Biol. 6(4), 318–327.
Khalil, H.K., 2002. Nonlinear Systems, 3rd edition. Prentice Hall, Upper Saddle River, New Jersey.
Kimball, S.R., Jefferson, L., 2000. Regulation of translation initiation in mammalian cells by amino acids. In: Sonenberg, N., Hershey, J., Mathews, M.B. (Eds.), Translational Control of Gene Expression. Translational Control. Cold Spring Harbor Laboratory Press, New York, pp. 561–579 (Chapter 16).
Kozak, M., October 1991. Structural features in eukaryotic mRNAs that modulate the initiation of translation. The Journal of Biological Chemistry 266(30), 19867–19870.
Lewis, J., Ames, B., 1972. Histidine regulation in Salmonella typhimurium. XI. The percentage of transfer RNA his charged in vivo and its relation to the repression of the histidine operon. Journal of Molecular Biology 66(1), 131–142.
MacKay, Li, Flory, Turcott, Law, Serikawa, Xu, Lee, Goodlett, Aebersold, Zhao, and Morris]MolCellProteomics:3:478 MacKay, V.L., Li, X., Flory, M.R., Turcott, E., Law, G.L., Serikawa, K.A., Xu, X.L., Lee, H., Goodlett, D.R., Aebersold, R., Zhao, L.P., Morris, D.R., 2004. Gene expression analyzed by high-resolution state array analysis and quantitative proteomics: Response of yeast to mating pheromone. Mol. Cell Proteomics 3(5), 478–489.
Mathews, D.H., Sabina, J., Zuker, M., Turner, D.H., 1999. Expanded sequence dependence of thermodynamic parameters improves prediction of RNA secondary structure. J. Mol. Biol. (288), 911–940.
Merrick, W.C., Hershey, J.W., 1996. The pathway and mechanism of eukaryotic protein synthesis. In: Hershey, J.W., Mathews, M.B., Sonenberg, N. (Eds.), Translational Control, vol. 1 of Translational Control. Cold Spring Harbor Laboratory Press, New York, pp. 31–69 (Chapter 2).
Merrick, W.C., Nyborg, J., 2000. The protein biosynthesis elongation cycle. In: Sonenberg, N., Hershey, J., Mathews, M.B. (Eds.), Translational Control of Gene Expresison. Cold Spring Harbor Laboratory Press, New York, pp. 89–125 (Chapter 3).
Mikami, S., Masutani, M., Sonenberg, N., Yokoyama, S., Imataka, H., April 2006. An efficient mammalian cell-free translation system supplemented with translation factors. Protein Expression and Purification 46(2), 348–357.
Raught, B., Gingras, A.C., Sonenberg, N., 2000. Regulation of ribosomal recruitment in eukaryotes. In: Sonenberg, N., Hershey, J., Mathews, M.B. (Eds.), Translational Control of Gene Expresison. Cold Spring Harbor Laboratory Press, New York, pp. 245–293 (Chapter 6).
Rowlands, A.G., Panniers, R., Henshaw, E.C., 1988. The catalytic mechanism of guanine nucleotide exchange factor action and competitive inhibition by phosphorylated eukaryotic initiation factor 2. J. Biol. Chem. 263(12), 5526–5533.
Scheuner, D., Mierde, D., Song, B., Flamez, D., Creemers, J., Tsukamoto, K., Ribick, M., Schuit, F., Kaufman, R., Jun 2005. Control of mRNA translation preserves endoplasmic reticulum function in beta cells and maintains glucose homeostasis. Natural Medicine 11(7), 757–64.
Surdin-Kerjan, Y., Cherest, H., Robichon-Szulmajster, H., 1973. Relationship between methionyl transfer ribonucleic acid cellular content and synthesis of methionine enzyme in Saccharomyces cerevisiae. J. Bacteriol. 113, 1156–1160.
Trachsel, H., 1996. Binding of Initiator Methionyl-t RNA to Ribosomes. In: Hershey, J.W., Mathews, M.B., Sonenberg, N. (Eds.), Translational Control. Translational Control of Gene Expression. Cold Spring Harbor Laboratory Press, New York, pp. 113–138 (Chapter 4).
Voet, D., 2004. Biochemistry, 3rd edition. John Wiley & sons, Inc., New York.
Wong, K.K.Y., Bouwer, H.G.A., Freitag, N.E., 2004. Evidence implicating the 5’ untranslated region of Listeria monocytogenes actA in the regulation of bacterial actin-based motility. Cell. Microbiol. 6(2), 155–166.
Author information
Authors and Affiliations
Corresponding author
Additional information
An erratum to this article can be found at http://dx.doi.org/10.1007/s11538-006-9179-4
Rights and permissions
About this article
Cite this article
Skjøndal-Bara, N., Morrisb, D.R. Dynamic Model of the Process of Protein Synthesis in Eukaryotic Cells. Bull. Math. Biol. 69, 361–393 (2007). https://doi.org/10.1007/s11538-006-9128-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11538-006-9128-2