Ribosome economics: Ribosome usage in translation initiation and elongation
Résumé
Proteins are the basis of cellular functions, yet key parameters regulating protein synthesis remain elusive. Understanding the fine mechanisms of regulation is a major goal of molecular and systems biology, and this knowledge will support many synthetic biology applications.
We have the ambitious goal of providing a biophysical modelling framework of one of the last steps in protein synthesis, namely mRNA translation. Our work focuses 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? We explain how the transcript efficiency can be dictated by ribosome abundances, codon usage and transcript length.
We propose analytical and simulation methods to investigate translation models based on an inhomogeneous exclusion process, the prototypical non-equilibrium traffic model in one dimension. We show that the first codons, together with the value of the initiation rate, are the main determinants of protein production. Finally, we interpret the obtained analytical results based on the evolutionary role of codons' choice for regulating translation rates and ribosome usage.