%0 Journal Article
%T Physical modeling of ribosomes along messenger RNA: estimating kinetic rates from ribosome profiling experiments with a ballistic model
%+ Laboratoire Charles Coulomb (L2C)
%+ Systèmes Complexes et Phénomènes Nonlinéaires (SCPN)
%+ Institut de Génomique Fonctionnelle (IGF)
%+ Méthodes et Algorithmes pour la Bioinformatique (LIRMM | MAB)
%A Chevalier, Carole
%A Dorignac, Jerome
%A Ibrahim, Yahaya
%A Choquet, Armelle
%A David, Alexandre
%A Ripoll, Julie
%A Rivals, Eric
%A Geniet, Frederic
%A Walliser, Nils-Ole
%A Palmeri, John
%A Parmeggiani, Andrea
%A Walter, Jean-Charles
%Z This project received partial financial support from the LabEx NUMEV (ANR-10-LABX- 0020) within the I-SITE MUSE of the University of Montpellier via the Flagship Project ‘‘Gene Expression Modeling" (NUMEV Etendard-2016-09).
%< avec comité de lecture
%Z L2C:22-142
%@ 1553-734X
%J PLoS Computational Biology
%I Public Library of Science
%V 19
%N 10
%P e1011522
%8 2023-10-20
%D 2023
%Z 2208.12576
%R 10.1371/journal.pcbi.1011522
%M 37862386
%Z Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph]Journal articles
%X Gene expression consists in 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 into polypeptide sequences of amino acids. Here, by taking into account messenger RNA degradation, we model the motion of ribosomes along messenger RNA 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 this case an inverse fit gives access to the kinetic rates: the position-dependent speeds and the entry rate of ribosomes onto messenger RNA. 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 messenger RNAs 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 messenger RNA, study the different regimes of degradation, and propose a criteria for the quality of the inverse fit. The proposed method provides a high sensitivity to the messenger RNA 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 messenger RNA degradation rate.
%G English
%2 https://hal.science/hal-03832368/document
%2 https://hal.science/hal-03832368/file/journal.pcbi.1011522.pdf
%L hal-03832368
%U https://hal.science/hal-03832368
%~ INSERM
%~ CNRS
%~ IGF
%~ L2C
%~ MAB
%~ LIRMM
%~ BS
%~ UNIV-MONTPELLIER
%~ ANR
%~ UM-2015-2021
%~ UM-EPE
%~ NUMEV