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
Link To Document :
بازگشت