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Physical modeling of ribosomes along messenger RNA: Estimating kinetic parameters from ribosome profiling experiments using a ballistic model

Gene expression is the synthesis of proteins from the information encoded on DNA. One of the two main steps of gene expression is the translation of messenger RNA (mRNA) into polypeptide sequences of amino acids. Here, by taking into account mRNA degradation, we model the motion of ribosomes along m...

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Autores principales: Chevalier, Carole, Dorignac, Jérôme, Ibrahim, Yahaya, Choquet, Armelle, David, Alexandre, Ripoll, Julie, Rivals, Eric, Geniet, Frédéric, Walliser, Nils-Ole, Palmeri, John, Parmeggiani, Andrea, Walter, Jean-Charles
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10659217/
https://www.ncbi.nlm.nih.gov/pubmed/37862386
http://dx.doi.org/10.1371/journal.pcbi.1011522
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author Chevalier, Carole
Dorignac, Jérôme
Ibrahim, Yahaya
Choquet, Armelle
David, Alexandre
Ripoll, Julie
Rivals, Eric
Geniet, Frédéric
Walliser, Nils-Ole
Palmeri, John
Parmeggiani, Andrea
Walter, Jean-Charles
author_facet Chevalier, Carole
Dorignac, Jérôme
Ibrahim, Yahaya
Choquet, Armelle
David, Alexandre
Ripoll, Julie
Rivals, Eric
Geniet, Frédéric
Walliser, Nils-Ole
Palmeri, John
Parmeggiani, Andrea
Walter, Jean-Charles
author_sort Chevalier, Carole
collection PubMed
description Gene expression is the synthesis of proteins from the information encoded on DNA. One of the two main steps of gene expression is the translation of messenger RNA (mRNA) into polypeptide sequences of amino acids. Here, by taking into account mRNA degradation, we model the motion of ribosomes along mRNA with a ballistic model where particles advance along a filament without excluded volume interactions. Unidirectional models of transport have previously been used to fit the average density of ribosomes obtained by the experimental ribo-sequencing (Ribo-seq) technique in order to obtain the kinetic rates. The degradation rate is not, however, accounted for and experimental data from different experiments are needed to have enough parameters for the fit. Here, we propose an entirely novel experimental setup and theoretical framework consisting in splitting the mRNAs into categories depending on the number of ribosomes from one to four. We solve analytically the ballistic model for a fixed number of ribosomes per mRNA, study the different regimes of degradation, and propose a criterion for the quality of the inverse fit. The proposed method provides a high sensitivity to the mRNA degradation rate. The additional equations coming from using the monosome (single ribosome) and polysome (arbitrary number) ribo-seq profiles enable us to determine all the kinetic rates in terms of the experimentally accessible mRNA degradation rate.
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spelling pubmed-106592172023-10-20 Physical modeling of ribosomes along messenger RNA: Estimating kinetic parameters from ribosome profiling experiments using a ballistic model Chevalier, Carole Dorignac, Jérôme Ibrahim, Yahaya Choquet, Armelle David, Alexandre Ripoll, Julie Rivals, Eric Geniet, Frédéric Walliser, Nils-Ole Palmeri, John Parmeggiani, Andrea Walter, Jean-Charles PLoS Comput Biol Research Article Gene expression is the synthesis of proteins from the information encoded on DNA. One of the two main steps of gene expression is the translation of messenger RNA (mRNA) into polypeptide sequences of amino acids. Here, by taking into account mRNA degradation, we model the motion of ribosomes along mRNA with a ballistic model where particles advance along a filament without excluded volume interactions. Unidirectional models of transport have previously been used to fit the average density of ribosomes obtained by the experimental ribo-sequencing (Ribo-seq) technique in order to obtain the kinetic rates. The degradation rate is not, however, accounted for and experimental data from different experiments are needed to have enough parameters for the fit. Here, we propose an entirely novel experimental setup and theoretical framework consisting in splitting the mRNAs into categories depending on the number of ribosomes from one to four. We solve analytically the ballistic model for a fixed number of ribosomes per mRNA, study the different regimes of degradation, and propose a criterion for the quality of the inverse fit. The proposed method provides a high sensitivity to the mRNA degradation rate. The additional equations coming from using the monosome (single ribosome) and polysome (arbitrary number) ribo-seq profiles enable us to determine all the kinetic rates in terms of the experimentally accessible mRNA degradation rate. Public Library of Science 2023-10-20 /pmc/articles/PMC10659217/ /pubmed/37862386 http://dx.doi.org/10.1371/journal.pcbi.1011522 Text en © 2023 Chevalier et al 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
Chevalier, Carole
Dorignac, Jérôme
Ibrahim, Yahaya
Choquet, Armelle
David, Alexandre
Ripoll, Julie
Rivals, Eric
Geniet, Frédéric
Walliser, Nils-Ole
Palmeri, John
Parmeggiani, Andrea
Walter, Jean-Charles
Physical modeling of ribosomes along messenger RNA: Estimating kinetic parameters from ribosome profiling experiments using a ballistic model
title Physical modeling of ribosomes along messenger RNA: Estimating kinetic parameters from ribosome profiling experiments using a ballistic model
title_full Physical modeling of ribosomes along messenger RNA: Estimating kinetic parameters from ribosome profiling experiments using a ballistic model
title_fullStr Physical modeling of ribosomes along messenger RNA: Estimating kinetic parameters from ribosome profiling experiments using a ballistic model
title_full_unstemmed Physical modeling of ribosomes along messenger RNA: Estimating kinetic parameters from ribosome profiling experiments using a ballistic model
title_short Physical modeling of ribosomes along messenger RNA: Estimating kinetic parameters from ribosome profiling experiments using a ballistic model
title_sort physical modeling of ribosomes along messenger rna: estimating kinetic parameters from ribosome profiling experiments using a ballistic model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10659217/
https://www.ncbi.nlm.nih.gov/pubmed/37862386
http://dx.doi.org/10.1371/journal.pcbi.1011522
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