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, see e.g. Lodish et al. (Molecular cell biology, 8th edn, W.H. Freeman and Company, San Francisco, 2016). In order to estimate the effect of cytoplasmic diffusion on the rate of translation, we consider a totally asymmetric simple exclusion process coupled to a finite diffusive reservoir, which we call the ribosome transport model with diffusion. 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 is not a rate limiting factor in translation initiation because diffusion is fast enough in biological cells.Graphic abstract
Highlights
Cells synthesize proteins by first transcribing the hereditary information encoded in genes into functional mRNA and subsequently by translating the mRNA nucleotide sequence into polypeptide sequences [1]
We introduce here the ribosome transport model with diffusion (RTD), a minimalistic model that allows us to study how diffusion determines the rate of protein synthesis
Using a mean-field approximation, we have derived the formula (12) for the current J in the RTD model, which describes the protein translation rate for one mRNA in a diffusive reservoir that contains a large number of ribosomes
Summary
Cells synthesize proteins by first transcribing the hereditary information encoded in genes into functional mRNA and subsequently by translating the mRNA nucleotide sequence into polypeptide sequences [1]. The translation of mRNA into a polypeptide sequence can be divided into three stages, namely the initiation, elongation and termination stages [1]. The ribosomal complex moves (or elongates) from the 5’ end towards the 3’ end of the mRNA while forming a polypeptide chain. In the final termination stage, the ribosome complex releases the polypeptide chain, unbinds from the mRNA and disassembles. Translation is mainly controlled at the initiation step, as it is the rate limiting step in translation [2,3,4,5]. Initiation is a complex process involving several molecular actors, and it is difficult to understand all the molecular mechanisms that are relevant for translation control. Coarse-grained mathematical modelling can uncover which physical mechanisms play a role in translation control
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