Translation with frameshifting of ribosome along mRNA transcript

TL;DR

This paper presents a theoretical model of ribosome frameshifting during translation, revealing how it affects translation efficiency and speed, and suggesting regulation strategies for optimal protein synthesis.

Contribution

It introduces a novel model incorporating ribosome frameshifting and attachment/detachment, extending existing translation models to better reflect biological reality.

Findings

Ribosome frameshifting can increase then decrease translation speed.

Optimal translation speed can be achieved by regulating initiation and detachment rates.

Traffic phenomena like shock waves can occur in ribosome movement along mRNA.

Abstract

Translation is an important process for prokaryotic and eukaryotic cells to produce necessary proteins for cell growth. Numerious experiments have been performed to explore the translational properties. Diverse models have also been developed to determine the biochemical mechanism of translation. However, to simplify the majority of the existing models, the frameshifting of ribosome along the mRNA transcript is neglected, which actually occurs in real cells and has been extensively experimentally studied. The frameshifting of ribosome evidently influences the efficiency and speed of translation, considering that the peptide chains synthesized by shifted ribosomes will not fold into functional proteins and will degrade rapidly. In this study, a theoretical model is presented to describe the translational process based on the model for totally asymmetric simple exclusion process. In this model, the frameshifting of the ribosome along the mRNA transcript and the attachment/detachment of the ribosome to/from the main body of mRNA codons during translation elongation process, are explicitly included. The results show that, with ribosome frameshifing, the speed of correctly synthesized peptide chains may increase first and then decrease with both the translation initiation rate $\alpha$ and the ribosome detachment rate $\omega_d$. This results indicates that regulating the translation process to reach maximal synthesized speed of proteins is theoretically feasible. Traffic-related problems of ribosome motion along the mRNA transcript are also addressed theoretically. Depending on parameter values, shock wave (or domain wall) may exist for ribosome probabilities along the mRNA.