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- Transcript length as a main determinant of mRNA translation efficiency hal link

Auteur(s): Ciandrini L.

Conference: Quantitative Methods in Gene Regulation III (Cambridge, GB, 2015-12-07)


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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 from a modeler’s point of view, on the role of translation initiation and how this step is mainly dictated by ribosome abundances, finite size effects and recycling. We propose an approach based on the standard exclusion process, 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 data, which are well reproduced qualitatively and quantitatively. The proposed mathematical framework thus 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.