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Evolutionary conservation of codon optimality reveals hidden signatures of cotranslational folding | Nature Structural & Molecular Biology
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Rare or nonoptimal codons that cause ribosomes to pause have been suggested to be important determinants of cotranslational folding. A revised translational efficiency scale, which considers tRNA abundance as well as codon usage and codon-tRNA interaction, now suggests a correlation between optimal or nonoptimal codon usage and secondary structure of the nascent polypeptide. The choice of codons can influence local translation kinetics during protein synthesis. Whether codon preference is linked to cotranslational regulation of polypeptide folding remains unclear. Here, we derive a revised translational efficiency scale that incorporates the competition between tRNA supply and demand. Applying this scale to ten closely related yeast species, we uncover the evolutionary conservation of codon optimality in eukaryotes. This analysis reveals universal patterns of conserved optimal and nonoptimal codons, often in clusters, which associate with the secondary structure of the translated polypeptides independent of the levels of expression. Our analysis suggests an evolved function for codon optimality in regulating the rhythm of elongation to facilitate cotranslational polypeptide folding, beyond its previously proposed role of adapting to the cost of expression. These findings establish how mRNA sequences are generally under selection to optimize the cotranslational folding of corresponding polypeptides.
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headline:Evolutionary conservation of codon optimality reveals hidden signatures of cotranslational folding
description:Rare or nonoptimal codons that cause ribosomes to pause have been suggested to be important determinants of cotranslational folding. A revised translational efficiency scale, which considers tRNA abundance as well as codon usage and codon-tRNA interaction, now suggests a correlation between optimal or nonoptimal codon usage and secondary structure of the nascent polypeptide. The choice of codons can influence local translation kinetics during protein synthesis. Whether codon preference is linked to cotranslational regulation of polypeptide folding remains unclear. Here, we derive a revised translational efficiency scale that incorporates the competition between tRNA supply and demand. Applying this scale to ten closely related yeast species, we uncover the evolutionary conservation of codon optimality in eukaryotes. This analysis reveals universal patterns of conserved optimal and nonoptimal codons, often in clusters, which associate with the secondary structure of the translated polypeptides independent of the levels of expression. Our analysis suggests an evolved function for codon optimality in regulating the rhythm of elongation to facilitate cotranslational polypeptide folding, beyond its previously proposed role of adapting to the cost of expression. These findings establish how mRNA sequences are generally under selection to optimize the cotranslational folding of corresponding polypeptides.
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