The combined influence of codon composition and tRNA copy number regulates translational efficiency by influencing synonymous nucleotide substitution.

Codon usage bias is an important genomic phenomenon, where highly expressed genes use optimal codons for smoother translation with high yield, facilitated by the cognate tRNAs. Here, we presented the tRNA co-adaptation index (co-AI) by correlating tRNA gene copy number and codon composition in Saccharomyces cerevisiae. We observed that this co-AI is positively correlated with protein abundance and translation rate. Considering nucleotide substitutions, co-AI influences synonymous substitutions more than gene expression and protein abundance, the most important determinants of evolutionary rate. Co-AI correlates positively with mRNA secondary structure stability and mRNA half-life, which may lead to protein accumulation under high co-AI. However, the highly expressed proteins encoded by high co-AI genes are assisted by molecular chaperones to attain their proper functional conformation and prevent accumulation.

The optimization of mRNA expression level by its intrinsic properties-Insights from codon usage pattern and structural stability of mRNA.

Codon usage bias (CUB) and mRNA structural stability are important intrinsic features of mRNA that correlate positively with mRNA expression level. However, it remains unclear whether the mRNA expression level can be regulated by adjusting these two parameters, influencing the mRNAs' structure. Here we explored the influence of CUB and mRNA structural stability on mRNA expression levels in Saccharomyces cerevisiae, using both wild type and computationally mutated mRNAs. Although in wild type, both CUB and mRNA stability positively regulate the mRNA expression level, any deviation from natural situation breaks such equilibrium. The naturally occurring codon composition is responsible for optimizing the mRNA expression, and under such composition, the mRNA structure having highest stability is selected by nature.