Basic, simple and extendable kinetic model of protein synthesis

TL;DR

This paper introduces a simple, extendable kinetic model of protein synthesis derived from detailed models, capable of analytical solutions and useful for understanding cellular translation dynamics.

Contribution

It presents a basic, analytically solvable kinetic model of protein synthesis that simplifies complex states and can be extended to include various biological phenomena.

Findings

Identifies critical parameters for protein synthesis with abundant ribosomes.

Demonstrates intrinsic bi-stability in ribosomal protein turnover.

Predicts minimal ribosome numbers needed for sustained protein synthesis.

Abstract

Protein synthesis is one of the most fundamental biological processes, which consumes a significant amount of cellular resources. Despite existence of multiple mathematical models of translation, varying in the level of mechanistical details, surprisingly, there is no basic and simple chemical kinetic model of this process, derived directly from the detailed kinetic model. One of the reasons for this is that the translation process is characterized by indefinite number of states, thanks to existence of polysomes. We bypass this difficulty by applying a trick consisting in lumping multiple states of translated mRNA into few dynamical variables and by introducing a variable describing the pool of translating ribosomes. The simplest model can be solved analytically under some assumptions. The basic and simple model can be extended, if necessary, to take into account various phenomena such as the interaction between translating ribosomes, limited amount of ribosomal units or regulation of translation by microRNA. The model can be used as a building block (translation module) for more complex models of cellular processes. We demonstrate the utility of the model in two examples. First, we determine the critical parameters of the single protein synthesis for the case when the ribosomal units are abundant. Second, we demonstrate intrinsic bi-stability in the dynamics of the ribosomal protein turnover and predict that a minimal number of ribosomes should pre-exists in a living cell to sustain its protein synthesis machinery, even in the absence of proliferation.