Totally asymmetric exclusion process with extended objects: A model for protein synthesis

Shaw, Leah B.; Zia, R. K. P.; Lee, Kelvin H.

doi:10.1103/physreve.68.021910

Cited by 326 publications

(335 citation statements)

References 45 publications

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“…7(a) and 8(a), the approximation works very well. Another quantity that we have numerically computed is the average probability distribution, Π n , of the total number of ribosomes, n as defined in (2). A plot of this quantity for (17), which provides a very good approximation to the data.…”

Section: Low Density (Ld) Casementioning

confidence: 99%

“…The theoretical challenge is to identify important mechanisms and develop simple models that capture the experimental results and have predictive power. The totally asymmetric simple exclusion process (TASEP) is a nonequilibrium lattice model that has been intensely studied in connection to mRNA translation [1][2][3][4][5]. TASEPs are interesting models in themselves and have emerged as a paradigm in nonequilibrium physics because they lead to nontrivial but analytically tractable behavior [6,7].…”

Section: Introductionmentioning

confidence: 99%

“…The effects of mRNA degradation have largely been overlooked in previous studies of dynamical models. Usually, it is assumed that a steady state average should reflect the experimental observations [2,3,5]. In reality, the cell extract is expected to contain mRNA of various ages, all of which will contribute to the average, see Fig.…”

Section: Introductionmentioning

confidence: 99%

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Translation by Ribosomes with mRNA Degradation: Exclusion Processes on Aging Tracks

2011

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We investigate the role of degradation of mRNA on protein synthesis using the totally asymmetric simple exclusion process (TASEP) as the underlying model for ribosome dynamics. mRNA degradation has a strong effect on the lifetime distribution of the mRNA, which in turn affects polysome statistics such as the number of ribosomes present on an mRNA strand of a given size. An average over mRNA of all ages is equivalent to an average over possible configurations of the corresponding TASEP-both before steady state and in steady state. To evaluate the relevant quantities for the translation problem, we first study the approach towards steady state of the TASEP, starting with an empty lattice representing an unloaded mRNA. When approaching the high density phase, the system shows two distinct phases with the entry and exit boundaries taking control of the density at their respective ends in the second phase. The approach towards the maximal current phase exhibits the surprising property that the ribosome entry flux can exceed the maximum possible steady state value. In all phases, the averaging over the mRNA age distribution shows a decrease in the average ribosome density profile as a function of distance from the entry boundary. For entry/exit parameters corresponding to the high density phase of TASEP, the average ribosome density profile also has a maximum near the exit end.

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Section: Low Density (Ld) Casementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Translation by Ribosomes with mRNA Degradation: Exclusion Processes on Aging Tracks

2011

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“…We refer to such collective movement of ribosomes on a mRNA strand as ribosome traffic because of its superficial similarity with vehicular traffic [22]. In most of the earlier theoretical studies of ribosome traffic, individual ribosomes have been modelled as hard rods and their steric interactions have been captured by mutual exclusion [23,24,25,26,27,28,29,30,31,32]. Thus, all those models may be regarded as totally asymmetric simple exclusion process (TASEP) for hard rods [33,34].…”

Section: Introductionmentioning

confidence: 99%

Stochastic kinetics of ribosomes: Single motor properties and collective behavior

Garai

Chowdhury

et al. 2009

Phys. Rev. E

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Synthesis of protein molecules in a cell are carried out by ribosomes. A ribosome can be regarded as a molecular motor which utilizes the input chemical energy to move on a messenger RNA (mRNA) track that also serves as a template for the polymerization of the corresponding protein. The forward movement, however, is characterized by an alternating sequence of translocation and pause. Using a quantitative model, which captures the mechanochemical cycle of an individual ribosome, we derive an exact analytical expression for the distribution of its dwell times at the successive positions on the mRNA track. Inverse of the average dwell time satisfies a "Michaelis-Menten-like" equation and is consistent with the general formula for the average velocity of a molecular motor with an unbranched mechano-chemical cycle. Extending this formula appropriately, we also derive the exact force-velocity relation for a ribosome. Often many ribosomes simultaneously move on the same mRNA track, while each synthesizes a copy of the same protein. We extend the model of a single ribosome by incorporating steric exclusion of different individuals on the same track. We draw the phase diagram of this model of ribosome traffic in 3-dimensional spaces spanned by experimentally controllable parameters. We suggest new experimental tests of our theoretical predictions.

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“…Eventually, this description needs to be expanded to a stochastic codon-based model. Such models can be formulated as Totally Asymmetric Simple Exclusion Process (Shaw et al, 2003;Chou and Lakatos, 2004;Shaw et al, 2004a). This would allow for a more detailed and realistic description of various aspects of translation (for example multiple codon coverage of ribosomes).…”

Section: Conclusion and Discussionmentioning

confidence: 99%

A mathematical modelling framework for elucidating the role of feedback control in translation termination

Silva

Krishnan

Betney

et al. 2010

Journal of Theoretical Biology

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Translation is the final stage of gene expression where messenger RNA is used as a template for protein polymerisation from appropriate amino acids. Release of the completed protein requires a release factor protein acting at the termination/stop codon to liberate it. In this paper we focus on a complex feedback control mechanism involved in the translation and synthesis of release factor proteins, which has been observed in different systems. These release factor proteins are involved in the termination stage of their own translation. Further, mutations in the release factor gene can result in a premature stop codon. In this case translation can result either in early termination and the production of a truncated protein or readthrough of the premature stop codon and production of the complete release factor protein. Thus during translation of the release factor mRNA containing a premature stop codon, the full length protein negatively regulates its production by its action on a premature stop codon, while positively regulating its production by its action on the regular stop codon. This paper develops a mathematical modelling framework to investigate this complex feedback control system involved in translation. A series of models is established to carefully investigate the role of individual mechanisms and how they work together. The steady state and dynamic behaviour of the resulting models are examined both analytically and numerically.

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Totally asymmetric exclusion process with extended objects: A model for protein synthesis

Cited by 326 publications

References 45 publications

Translation by Ribosomes with mRNA Degradation: Exclusion Processes on Aging Tracks

Translation by Ribosomes with mRNA Degradation: Exclusion Processes on Aging Tracks

Stochastic kinetics of ribosomes: Single motor properties and collective behavior

A mathematical modelling framework for elucidating the role of feedback control in translation termination

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