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. Author manuscript; available in PMC: 2021 Jul 16.
Published in final edited form as: Annu Rev Biochem. 2021 Jan 13;90:375–401. doi: 10.1146/annurev-biochem-071320-112701

Table 1.

Translation-dependent and translation-independent effects of codon usage

Translation-dependent cell function Effect of codon usage
Translation elongation Optimal codons speed up the translation elongation rate, while rare codons slow it down, due to differential expression levels of corresponding tRNAs.
Translation efficiency Codon usage regulates protein synthesis by affecting the amount of protein produced per mRNA in a given time.
Translation initiation Rare codons can cause ribosome stalling and may inhibit translation initiation, whereas optimal codons may result in rapid liberation of start codons and high initiation rates.
Translation fidelity Codon usage regulates the fidelity of amino acid incorporation and maintenance of the translation reading frame.
Premature termination Rare codons can cause ribosome stalling and promote eRF1-mediated premature translation termination at sense codons.
tRNA expression, modification, and charging Differential tRNA expression levels and tRNA modification and charging levels determine codon usage-biased mRNA translation in different tissues and cell types.
Cotranslational protein folding The effect of codon usage on translation elongation speed affects the time available for the cotranslational protein folding process, thus affecting protein structure and function.
Cotranslational mRNA decay Rare codons can cause ribosome stalling and promote translation-dependent mRNA decay mediated by the CCR4-NOT complex.
Translation-independent cell function Effect of codon usage
Transcription Codon optimality determines gene transcription levels from fungi to mammalian cells.
Chromatin structure Codon composition affects chromatin structures by affecting transcription activation and suppression-related histone modification marks.
Transcription termination Rare codons promote premature transcription termination through the formation of noncanonical poly(A) signals within open reading frames.
mRNA structure Codon usage changes can result in mRNA structure changes, which may influence RNA stability and translation.
Splicing Codon composition can influence splice site and exonic splicing enhancer and silencer sequences.
mRNA localization/transport Codon usage profiles can influence mRNA cellular transport and localization.
mRNA toxicity mRNAs with certain codon usage profiles can cause cellular toxicity in Escherischia coli.