Ribosome collisions and Translation efficiency: Optimization by codon usage and mRNA destabilization

TL;DR

This study models ribosome traffic during translation, revealing how codon usage and mRNA stability minimize collisions and optimize translation efficiency in bacteria.

Contribution

It introduces a stochastic traffic model of translation that explains how codon choice and mRNA destabilization reduce ribosome collisions and improve efficiency.

Findings

Ribosome collisions are inevitable in stochastic translation.

mRNA instability and codon optimization at the start reduce collisions.

The model estimates initiation rates and occlusion times in vivo.

Abstract

Individual mRNAs are translated by multiple ribosomes that initiate translation with a few seconds interval. The ribosome speed is codon dependant, and ribosome queuing has been suggested to explain specific data for translation of some mRNAs in vivo. By modelling the stochastic translation process as a traffic problem, we here analyze conditions and consequences of collisions and queuing. The model allowed us to determine the on-rate (0.8 to 1.1 initiations per sec) and the time (1 sec) the preceding ribosome occludes initiation for Escherichia coli lacZ mRNA in vivo. We find that ribosome collisions and queues are inevitable consequences of a stochastic translation mechanism that reduce the translation efficiency substantially on natural mRNAs. The cells minimize collisions by having its mRNAs being unstable and by a highly selected codon usage in the start of the mRNA. The cost of mRNA breakdown is offset by the concomitant increase in translational efficiency.