• DocumentCode
    20290
  • Title

    Explicit Expression for the Steady-State Translation Rate in the Infinite-Dimensional Homogeneous Ribosome Flow Model

  • Author

    Zarai, Yoram ; Margaliot, Michael ; Tuller, Tamir

  • Author_Institution
    Sch. of Electr. Eng., Tel-Aviv Univ., Tel-Aviv, Israel
  • Volume
    10
  • Issue
    5
  • fYear
    2013
  • fDate
    Sept.-Oct. 2013
  • Firstpage
    1322
  • Lastpage
    1328
  • Abstract
    Gene translation is a central stage in the intracellular process of protein synthesis. Gene translation proceeds in three major stages: initiation, elongation, and termination. During the elongation step, ribosomes (intracellular macromolecules) link amino acids together in the order specified by messenger RNA (mRNA) molecules. The homogeneous ribosome flow model (HRFM) is a mathematical model of translation-elongation under the assumption of constant elongation rate along the mRNA sequence. The HRFM includes n first-order nonlinear ordinary differential equations, where n represents the length of the mRNA sequence, and two positive parameters: ribosomal initiation rate and the (constant) elongation rate. Here, we analyze the HRFM when n goes to infinity and derive a simple expression for the steady-state protein synthesis rate. We also derive bounds that show that the behavior of the HRFM for finite, and relatively small, values of n is already in good agreement with the closed-form result in the infinite-dimensional case. For example, for n = 15, the relative error is already less than 4 percent. Our results can, thus, be used in practice for analyzing the behavior of finite-dimensional HRFMs that model translation. To demonstrate this, we apply our approach to estimate the mean initiation rate in M. musculus, finding it to be around 0.17 codons per second.
  • Keywords
    RNA; biochemistry; biomechanics; cellular transport; elongation; genetics; molecular biophysics; nonlinear differential equations; physiological models; proteins; HRFM behavior; amino acid; constant elongation rate; explicit expression; finite-dimensional HRFM; gene elongation; gene initiation; gene termination; gene translation; infinite-dimensional case; infinite-dimensional homogeneous ribosome flow model; intracellular macromolecules; intracellular process; mRNA sequence length; mathematical model; messenger RNA molecules; model translation; musculus; n first-order nonlinear ordinary differential equations; relative error; ribosomal elongation rate; ribosomal initiation rate; steady-state protein synthesis rate; steady-state translation rate; translation-elongation; Biological system modeling; Computational modeling; Genetics; Mathematical model; Proteins; Steady-state; Gene translation; computational models; monotone dynamical systems; periodic continued fractions; systems biology;
  • fLanguage
    English
  • Journal_Title
    Computational Biology and Bioinformatics, IEEE/ACM Transactions on
  • Publisher
    ieee
  • ISSN
    1545-5963
  • Type

    jour

  • DOI
    10.1109/TCBB.2013.120
  • Filename
    6606794