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- A quantitative view on mRNA translation: the relative role of initiation and elongation hal link

Auteur(s): Ciandrini L.

Conference: Quantitative Laws II: Physiology, ecology, interaction structures, collective behavior (Como, IT, 2016-06-13)


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Résumé:

Proteins are the basis of cellular functions, yet key parameters regulating protein synthesis remain elusive. Understanding the fine mechanisms of this regulation is a major goal of molecular and systems biology, and this knowledge will support many “synthetic biological” applications.We have the ambitious goal of providing a comprehensive modeling framework of one of the last steps of protein synthesis, namely mRNA translation. In this presentation I will focus on translation initiation and elongation, which relative role is highly debated in the literature (is the ribosome recruitment or the codon bias determining the expression of a gene?). Here I will explain how the transcript efficiency can be dictated by ribosome abundances, codon usage and transcript length. We propose an approach based on the standard exclusion process, a prototypic lattice gas model. This mathematical framework considers long-range dynamical effects often neglected in standard translation models.The model is compared to experimental ribosome density and gene expression data, which are well reproduced qualitatively and quantitatively. The proposed mathematical framework also describes the origins of the well-known and yet not understood relation between transcript efficiency and its length. We also speculate on the role of transcript length in the competition for ribosomes among different mRNAs.