A code within the genetic code: codon usage regulates co-translational protein folding

Yi Liu

doi:10.1186/s12964-020-00642-6

Abstract

The genetic code is degenerate, and most amino acids are encoded by two to six synonymous codons. Codon usage bias, the preference for certain synonymous codons, is a universal feature of all genomes examined. Synonymous codon mutations were previously thought to be silent; however, a growing body evidence now shows that codon usage regulates protein structure and gene expression through effects on co-translational protein folding, translation efficiency and accuracy, mRNA stability, and transcription. Codon usage regulates the speed of translation elongation, resulting in non-uniform ribosome decoding rates on mRNAs during translation that is adapted to co-translational protein folding process. Biochemical and genetic evidence demonstrate that codon usage plays an important role in regulating protein folding and function in both prokaryotic and eukaryotic organisms. Certain protein structural types are more sensitive than others to the effects of codon usage on protein folding, and predicted intrinsically disordered domains are more prone to misfolding caused by codon usage changes than other domain types. Bioinformatic analyses revealed that gene codon usage correlates with different protein structures in diverse organisms, indicating the existence of a codon usage code for co-translational protein folding. This review focuses on recent literature on the role and mechanism of codon usage in regulating translation kinetics and co-translational protein folding.5xoCminnRXUHneYwYekFPKVideo abstract

Highlights

Of the 20 standard amino acids, 18 can be encoded by two to six synonymous codons
We measured the time of first appearance of luciferase signal from mRNA templates encoding luciferase with different codon usage profiles, our results demonstrated clearly that preferred codons speed up rate of translation elongation, whereas rare codons slow translation elongation in both systems (Fig. 1b)
A growing body of biochemical, genetic, and bioinformatic evidence indicates that the non-uniform decoding rate across mRNAs mediated by codon usage represents a “code” within genetic codons that promote optimal cotranslational protein folding process

Summary

Introduction

Of the 20 standard amino acids, 18 can be encoded by two to six synonymous codons. Preferential use of certain synonymous codons, a phenomenon called codon usage bias, has been found in all genomes evaluated [1,2,3,4]. In addition to the roles of codon usage in regulating gene expression, a large body of biochemical and bioinformatic evidence has established that co-translational protein folding is influenced by codon usage [5, 13, 20, 29, 50, 51].

Results

Conclusion