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- PHYSICAL MODELING OF TRANSLATION WITH A BALLISTIC MODEL: APPLICATION TO THE ESTIMATION OF THE KINETIC PARAMETERS FROM RIBOSOME SEQUENCING EXPERIMENTS

Auteur(s): Chevalier C., Dorignac J., Ibrahim Yahaya, Choquet Armelle, David Alexandre, Ripoll Julie, Rivals Eric, Geniet F., Walliser N.-O., Palmeri J., Parmeggiani A., Walter J.-C.

(Affiches/Poster) IPOLS (Montpellier, FR), 2022-06-01


Résumé:

Abstract : 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 (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 ribosome 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 into mRNA. 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 analytically solve 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 enables us to determine all the kinetic rates in terms of the experimentally accessible mRNA degradation rate.