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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2023
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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. |
format | Online Article Text |
id | pubmed-10659217 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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