Fluctuations in protein synthesis from a single RNA template: stochastic kinetics of ribosomes

TL;DR

This paper models the stochastic kinetics of ribosomes during protein synthesis, predicting dwell time distributions that align with experimental data and highlighting the influence of gene sequence variations on translation noise.

Contribution

It introduces a detailed stochastic model of ribosome translation that incorporates mechano-chemistry and steric interactions, providing new predictions for dwell time distributions.

Findings

Predicted dwell time distribution matches experimental data.

Sequence inhomogeneities affect translation fluctuations.

Model captures both mechano-chemistry and steric effects.

Abstract

Proteins are polymerized by cyclic machines called ribosome which use their messenger RNA (mRNA) track also as the corresponding template and the process is called translation. We explore, in depth and detail, the stochastic nature of the translation. We compute various distributions associated with the translation process; one of them, namely dwell time distribution, has been measured in recent single ribosome experiments (Wen et al. Nature {\bf 452}, 598 (2008)). The form of this distribution predicted by our theory is consistent with that extracted from the experimental data. For our quantitative calculations, we use a model that captures both the mechano-chemistry of each individual ribosome as well as their steric interactions. We also demonstrate the effects of the sequence inhomogeneities of real genes on the fluctuations and noise in translation. In principle, our new predictions can be tested by carrying out {\it in-vitro} experiments.