Modelling the effect of ribosome mobility on the rate of protein synthesis

TL;DR

This paper models how ribosome mobility affects protein synthesis rates, concluding that cytoplasmic diffusion is sufficiently fast and does not limit translation initiation, using a coupled TASEP-diffusion model validated by simulations.

Contribution

It introduces the Ribosome Transport model with Diffusion (RTD), combining TASEP with finite diffusion to analytically estimate translation rates.

Findings

Diffusion does not significantly control translation initiation rates.

Derived an analytical expression linking diffusion constant to protein synthesis rate.

Validated model results with continuous-time Monte Carlo simulations.

Abstract

Translation is one of the main steps in the synthesis of proteins. It consists of ribosomes that translate sequences of nucleotides encoded on mRNA into polypeptide sequences of amino acids. Ribosomes bound to mRNA move unidirectionally, while unbound ribosomes diffuse in the cytoplasm. It has been hypothesized that finite diffusion of ribosomes plays an important role in ribosome recycling and that mRNA circularization enhances the efficiency of translation. In order to estimate the effect of cytoplasmic diffusion on the rate of translation, we consider a Totally Asymmetric Simple Exclusion Process (TASEP) coupled to a finite diffusive reservoir, which we call the Ribosome Transport model with Diffusion (RTD). In this model, we derive an analytical expression for the rate of protein synthesis as a function of the diffusion constant of ribosomes, which is corroborated with results from continuous-time Monte Carlo simulations. Using a wide range of biological relevant parameters, we conclude that diffusion in biological cells is fast enough so that it does not play a role in controlling the rate of translation initiation.