Sensitivity of mRNA Translation

Sensitivity of mRNA Translation

Using the dynamic mean-field approximation of the totally asymmetric simple exclusion process (TASEP), we investigate the effect of small changes in the initiation, elongation, and termination rates along the mRNA strand on the steady-state protein translation rate. We show that the sensitivity of m...

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Main Authors: Poker, Gilad, Margaliot, Michael, Tuller, Tamir
Format: Online
Language:English
Published: Nature Publishing Group 2015
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4523843/
id pubmed-4523843
recordtype oai_dc
spelling pubmed-45238432015-08-05 Sensitivity of mRNA Translation Poker, Gilad Margaliot, Michael Tuller, Tamir Article Using the dynamic mean-field approximation of the totally asymmetric simple exclusion process (TASEP), we investigate the effect of small changes in the initiation, elongation, and termination rates along the mRNA strand on the steady-state protein translation rate. We show that the sensitivity of mRNA translation is equal to the sensitivity of the maximal eigenvalue of a symmetric, nonnegative, tridiagonal, and irreducible matrix. This leads to new analytical results as well as efficient numerical schemes that are applicable for large-scale models. Our results show that in the usual endogenous case, when initiation is more rate-limiting than elongation, the sensitivity of the translation rate to small mutations rapidly increases towards the 5′ end of the ORF. When the initiation rate is high, as may be the case for highly expressed and/or heterologous optimized genes, the maximal sensitivity is with respect to the elongation rates at the middle of the mRNA strand. We also show that the maximal possible effect of a small increase/decrease in any of the rates along the mRNA is an increase/decrease of the same magnitude in the translation rate. These results are in agreement with previous molecular evolutionary and synthetic biology experimental studies. Nature Publishing Group 2015-08-04 /pmc/articles/PMC4523843/ /pubmed/26238363 http://dx.doi.org/10.1038/srep12795 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Poker, Gilad
Margaliot, Michael
Tuller, Tamir
spellingShingle Poker, Gilad
Margaliot, Michael
Tuller, Tamir
Sensitivity of mRNA Translation
author_facet Poker, Gilad
Margaliot, Michael
Tuller, Tamir
author_sort Poker, Gilad
title Sensitivity of mRNA Translation
title_short Sensitivity of mRNA Translation
title_full Sensitivity of mRNA Translation
title_fullStr Sensitivity of mRNA Translation
title_full_unstemmed Sensitivity of mRNA Translation
title_sort sensitivity of mrna translation
description Using the dynamic mean-field approximation of the totally asymmetric simple exclusion process (TASEP), we investigate the effect of small changes in the initiation, elongation, and termination rates along the mRNA strand on the steady-state protein translation rate. We show that the sensitivity of mRNA translation is equal to the sensitivity of the maximal eigenvalue of a symmetric, nonnegative, tridiagonal, and irreducible matrix. This leads to new analytical results as well as efficient numerical schemes that are applicable for large-scale models. Our results show that in the usual endogenous case, when initiation is more rate-limiting than elongation, the sensitivity of the translation rate to small mutations rapidly increases towards the 5′ end of the ORF. When the initiation rate is high, as may be the case for highly expressed and/or heterologous optimized genes, the maximal sensitivity is with respect to the elongation rates at the middle of the mRNA strand. We also show that the maximal possible effect of a small increase/decrease in any of the rates along the mRNA is an increase/decrease of the same magnitude in the translation rate. These results are in agreement with previous molecular evolutionary and synthetic biology experimental studies.
publisher Nature Publishing Group
publishDate 2015
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4523843/
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