Control of ribosome traffic by position-dependent choice of synonymous codons

TL;DR

This paper investigates how the choice of synonymous codons in mRNA sequences influences ribosome traffic, affecting translation efficiency and cellular growth, using a model based on experimental data.

Contribution

It introduces a model that links codon choice to ribosome traffic, demonstrating that wild type sequences can reduce collisions and optimize translation.

Findings

Wild type sequences tend to reduce ribosome collisions.

Sequences with high codon bias optimize translation efficiency.

Codon choice impacts cellular growth and survival.

Abstract

Messenger RNA encodes a sequence of amino acids by using codons. For most amino acids there are multiple synonymous codons that can encode the amino acid. The translation speed can vary from one codon to another, thus there is room for changing the ribosome speed while keeping the amino acid sequence and hence the resulting protein. Recently, it has been noticed that the choice of the synonymous codon, via the resulting distribution of slow- and fast-translated codons, affects not only on the average speed of one ribosome translating the messenger RNA (mRNA) but also might have an effect on nearby ribosomes by affecting the appearance of "traffic jams" where multiple ribosomes collide and form queues. To test this "context effect" further, we here investigate the effect of the sequence of synonymous codons on the ribosome traffic by using a ribosome traffic model with codon-dependent rates, estimated from experiments. We compare the ribosome traffic on wild type sequences and sequences where the synonymous codons were swapped randomly. By simulating translation of 87 genes, we demonstrate that the wild type sequences, especially those with a high bias in codon usage, tend to have the ability to reduce ribosome collisions, hence optimizing the cellular investment in the translation apparatus. The magnitude of such reduction of the translation time might have a significant impact on the cellular growth rate and thereby have importance for the survival of the species.