• Physique/Physique/Biophysique
  
• Physique/Matière Condensée/Matière Molle
  
• Physique/Matière Condensée/Mécanique statistique
  

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.

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 differentexperiments 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.

Translation of messenger RNA (mRNA) leads to the production of proteins and is the last step of gene expression in cells. The dysregulation of translation can lead to all illnesses linked to the dysregulation of protein production, like cancer and neurodegenerative diseases.About ten years ago, a ribosomal density mapping strategy (Ribo-seq) was developed. The time is therefore ripe to apply theoretical physicsmethods to study translation. We model the movement of ribosomes on mRNA using the Totally Asymmetric Simple Exclusion Process (TASEP) which is an out of equilibrium one dimensional directed transport model. With Monte Carlo simulations and a mean field approach, we propose a way to calculate the speed of ribosomes from experimental data. Moreover, we provide preliminary results concerning the correlation between the speed of ribosomes and the occurrence rate of codons (RSCU).