Analysis of the association between codon optimality and mRNA stability in Schizosaccharomyces pombe

Recent experiments have shown that codon optimality is a major determinant of mRNA stability in Saccharomyces cerevisiae and that this phenomenon may be conserved in Escherichia coli and some metazoans, although work in Neurospora crassa is not consistent with this model.

We examined the association between codon optimality and mRNA stability in the fission yeast Schizosaccharomyces pombe. Our analysis revealed the following points. First, we observe a genome-wide association between codon optimality and mRNA stability also in S. pombe, suggesting evolutionary conservation of the phenomenon. Second, in both S. pombe and S. cerevisiae, mRNA synthesis rates are also correlated at the genome-wide analysis with codon optimality, suggesting that the long-appreciated association between codon optimality and mRNA abundance is due to regulation of both mRNA synthesis and degradation. However, when we examined correlation of codon optimality and either mRNA half-lives or synthesis rates controlling for mRNA abundance, codon optimality was still positively correlated with mRNA half-lives in S. cerevisiae, but the association was no longer significant for mRNA half-lives in S. pombe or for synthesis rates in either organism. This illustrates how only the pairwise analysis of multiple correlating variables may limit these types of analyses. Finally, in S. pombe, codon optimality is associated with known DNA/RNA sequence motifs that are associated with mRNA production/stability, suggesting these two features have been under similar selective pressures for optimal gene expression.

Consistent with the emerging body of studies, this study suggests that the association between codon optimality and mRNA stability may be a broadly conserved phenomenon. It also suggests that the association can be explained at least in part by independent adaptations of codon optimality and other transcript features for elevated expression during evolution.