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Modelling ribosome kinetics and translational control on dynamic mRNA

The control of protein synthesis and the overall levels of various proteins in the cell is critical for achieving homoeostasis. Regulation of protein levels can occur at the transcriptional level, where the total number of messenger RNAs in the overall transcriptome are controlled, or at the transla...

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Autor principal: Dykeman, Eric C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9894550/
https://www.ncbi.nlm.nih.gov/pubmed/36689464
http://dx.doi.org/10.1371/journal.pcbi.1010870
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author Dykeman, Eric C.
author_facet Dykeman, Eric C.
author_sort Dykeman, Eric C.
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description The control of protein synthesis and the overall levels of various proteins in the cell is critical for achieving homoeostasis. Regulation of protein levels can occur at the transcriptional level, where the total number of messenger RNAs in the overall transcriptome are controlled, or at the translational level, where interactions of proteins and ribosomes with the messenger RNA determine protein translational efficiency. Although transcriptional control of mRNA levels is the most commonly used regulatory control mechanism in cells, positive-sense single-stranded RNA viruses often utilise translational control mechanisms to regulate their proteins in the host cell. Here I detail a computational method for stochastically simulating protein synthesis on a dynamic messenger RNA using the Gillespie algorithm, where the mRNA is allowed to co-translationally fold in response to ribosome movement. Applying the model to the test case of the bacteriophage MS2 virus, I show that the models ability to accurately reproduce experimental measurements of coat protein production and translational repression of the viral RNA dependant RNA polymerase at high coat protein concentrations. The computational techniques reported here open up the potential to examine the infection dynamics of a ssRNA virus in a host cell at the level of the genomic RNA, as well as examine general translation control mechanisms present in polycistronic mRNAs.
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spelling pubmed-98945502023-02-03 Modelling ribosome kinetics and translational control on dynamic mRNA Dykeman, Eric C. PLoS Comput Biol Research Article The control of protein synthesis and the overall levels of various proteins in the cell is critical for achieving homoeostasis. Regulation of protein levels can occur at the transcriptional level, where the total number of messenger RNAs in the overall transcriptome are controlled, or at the translational level, where interactions of proteins and ribosomes with the messenger RNA determine protein translational efficiency. Although transcriptional control of mRNA levels is the most commonly used regulatory control mechanism in cells, positive-sense single-stranded RNA viruses often utilise translational control mechanisms to regulate their proteins in the host cell. Here I detail a computational method for stochastically simulating protein synthesis on a dynamic messenger RNA using the Gillespie algorithm, where the mRNA is allowed to co-translationally fold in response to ribosome movement. Applying the model to the test case of the bacteriophage MS2 virus, I show that the models ability to accurately reproduce experimental measurements of coat protein production and translational repression of the viral RNA dependant RNA polymerase at high coat protein concentrations. The computational techniques reported here open up the potential to examine the infection dynamics of a ssRNA virus in a host cell at the level of the genomic RNA, as well as examine general translation control mechanisms present in polycistronic mRNAs. Public Library of Science 2023-01-23 /pmc/articles/PMC9894550/ /pubmed/36689464 http://dx.doi.org/10.1371/journal.pcbi.1010870 Text en © 2023 Eric C. Dykeman https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Dykeman, Eric C.
Modelling ribosome kinetics and translational control on dynamic mRNA
title Modelling ribosome kinetics and translational control on dynamic mRNA
title_full Modelling ribosome kinetics and translational control on dynamic mRNA
title_fullStr Modelling ribosome kinetics and translational control on dynamic mRNA
title_full_unstemmed Modelling ribosome kinetics and translational control on dynamic mRNA
title_short Modelling ribosome kinetics and translational control on dynamic mRNA
title_sort modelling ribosome kinetics and translational control on dynamic mrna
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9894550/
https://www.ncbi.nlm.nih.gov/pubmed/36689464
http://dx.doi.org/10.1371/journal.pcbi.1010870
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