Ref HAL: hal-01737998_v1
Ref Arxiv: 1803.00887
DOI: 10.1103/PhysRevE.97.052139
WoS: 000433291900005
Ref. & Cit.: NASA ADS
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7 Citations
Résumé:

We develop a power series method for the nonequilibrium steady state of the inhomogeneous one-dimensional totally asymmetric simple exclusion process (TASEP) in contact with two particle reservoirs and with site-dependent hopping rates in the bulk. The power series is performed in the entrance or exit rates governing particle exchange with the reservoirs, and the corresponding particle current is computed analytically up to the cubic term in the entry or exit rate, respectively. We also show how to compute higher-order terms using combinatorial objects known as Young tableaux. Our results address the long outstanding problem of finding the exact nonequilibrium steady state of the inhomogeneous TASEP. The findings are particularly relevant to the modelling of mRNA translation in which the rate of translation initiation, corresponding to the entrance rate in the TASEP, is typically small.

Ref HAL: hal-01939022_v1
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Résumé:

In this short talk I will focus on mRNA, one of the last step of protein synthesis often neglected. I will introduce a quantitative model based on a Totally Asymmetric Simple Exclusion Process and integrate experimental data to the model to estimate translation rates previously undetermined.

Ref HAL: hal-01938988_v1
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Résumé:

Existing evidence such as codon usage bias suggests that protein translation of fast-growing organisms has been optimised for accuracy and better yield. One possibility for optimisation stems from the fact that different codons are translated at different rates. Common measures for optimal codon choice, which ignore the dynamics of this process, have so far had mixed success in predicting protein levels. Recent advances in experimental techniques such as ribosome profiling allow us to study dynamical details of this intricate process and theoretical modelling is required to interpret the new data. In this work we study a kinetic model for translation that takes into account stochastic movement of individual ribosomes along the mRNA molecule. Unlike previous studies of this and similar models that were limited to numerical simulations, we develop a novel mathematical method to find the steady state solution when the translation initiation is a rate-limiting step. This allows us, for the first time, to find an analytic prediction for the translation rate and ribosome density. We use these predictions to address some of the long-standing controversies surrounding the determinants of translation efficiency.

Ref HAL: hal-01938973_v1
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Résumé:

rotein synthesis rates are determined, at the translational level, by properties of the transcript’s sequence. The e ciency of an mRNA can be tuned by varying the ribosome binding sites controlling the recruitment of the ribosomes, or the codon usage establishing the speed of protein elongation. In this work we propose transcript length as a further key determinant of translation e ciency. Based on a physical model that considers the kinetics of ribosomes advancing on the mRNA and di using in its surrounding, as well as mRNA circularisation and ribosome drop-o , we explain how the transcript length may play a central role in establishing ribosome recruitment and the overall translation rate of an mRNA. According to our results, the proximity of the 3′ end to the ribosomal recruitment site of the mRNA could induce a feedback in the translation process that would favour the recycling of ribosomes. We also demonstrate how this process may be involved in shaping the experimental ribosome density-gene length dependence. Finally, we argue that cells could exploit this mechanism to adjust and balance the usage of its ribosomal resources.

Ref HAL: hal-01938945_v1
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Résumé:

Protein synthesis rates are determined, at the translational level, by properties of the transcript’s sequence. The efficiency of an mRNA can be tuned by varying the ribosome binding sites controlling the recruitment of the ribosomes, or the codon usage establishing the speed of protein elongation. In this work we promote transcript length as a further key determinant of translation efficiency. Based on a physical model that considers the kinetics ofribosomes advancing on the mRNA and diffusing in its surrounding, we explain how the transcript length might play a central role in establishing ribosome recruitment and the overall translation rate of an mRNA. We also demonstrate how this process might be involved in shaping the experimental ribosome density-gene length dependence. Finally, we argue that cells could exploit this mechanism to adjust and balance the usage of its ribosomal resources.

Ref HAL: hal-01585262_v1
DOI: 10.1038/s41598-017-17618-1
WoS: 000417689400033
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14 Citations
Résumé:

Protein synthesis rates are determined, at the translational level, by properties of the transcript's sequence. The efficiency of an mRNA can be tuned by varying the ribosome binding sites controlling the recruitment of the ribosomes, or the codon usage establishing the speed of protein elongation.In this work we propose transcript length as a further key determinant of translation efficiency. Based on a physical model that considers the kinetics of ribosomes advancing on the mRNA and diffusing in its surrounding, as well as mRNA circularisation and ribosome drop-off, we explain how the transcript length may play a central role in establishing ribosome recruitment and the overall translation rate of an mRNA. According to our results, the proximity of the 3' end to the ribosomal recruitment site of the mRNA could induce a feedback in the translation process that would favour the recycling of ribosomes.We also demonstrate how this process may be involved in shaping the experimental ribosome density-gene length dependence. Finally, we argue that cells could exploit this mechanism to adjust and balance the usage of its ribosomal resources.