Abstract
BackgroundEvidence in diverse organisms suggests that codon optimality is a major determinant of mRNA translation and degradation. Codon optimality is thought to act by modulating the efficiency of ribosome elongation. In Saccharomyces cerevisiae, a recent study has identified 17 adjacent codon pairs that mediate strong inhibition of translation elongation. However, relationships between the inhibitory codon pairs and other aspects of gene expression are unknown.ResultsTo gain insights into how the inhibitory codon pairs may affect aspects of gene expression, we utilized existing datasets to conduct genome-scale analyses in S. cerevisiae. Our analysis revealed the following points. First, the inhibitory codon pairs are significantly associated with faster mRNA decay. The association is not solely due to the content of nucleotides, individual codons, or dipeptides encoded by the inhibitory codon pairs. Second, the inhibitory codon pairs cannot fully explain the previously known relationship of codon optimality with mRNA stability, suggesting that optimality of individual codons and properties of adjacent codon pairs both contribute to gene regulation. Finally, although the inhibitory codon pairs are associated with slower mRNA synthesis and protein instability, the associations can be attributed to usage bias in individual codons.ConclusionsThis study suggests an association of inhibitory codon pairs with mRNA stability and thus another layer of complexity in the codon-mediated gene regulation.
Highlights
Evidence in diverse organisms suggests that codon optimality is a major determinant of mRNA translation and degradation
The inhibitory codon pairs are associated with inefficient synthesis and instability of mRNA It has been shown that genes with the inhibitory codon pairs are enriched in genes whose mRNA abundance is low [11]
Since mRNA abundance is determined by rates of mRNA synthesis and decay, we examined whether the previously identified 17 inhibitory codon pairs (1) are associated with mRNA synthesis and/or decay
Summary
Evidence in diverse organisms suggests that codon optimality is a major determinant of mRNA translation and degradation. In Saccharomyces cerevisiae, a recent study has identified 17 adjacent codon pairs that mediate strong inhibition of translation elongation. Until a recent study by Coller and colleagues [4], it was not appreciated that subtle differences in the rates of translation elongation due to specific codons, which can be indicated by “codon optimality,” would contribute in a general manner to defining mRNA decay rates. Data suggest that the codon-mediated mRNA decay is accompanied by a reduction in translation efficiency, defined as protein synthesis rates per mRNA [4, 7, 9], which may result from a decrease in translation initiation rate [10]
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