A universal trend of reduced mRNA stability near the translation-initiation site in prokaryotes and eukaryotes

Abstract

Recent studies have suggested that the thermodynamic stability of mRNA secondary structure near the start codon can regulate translation efficiency in Escherichia coli, and that translation is more efficient the less stable the secondary structure. We survey the complete genomes of 340 species for signals of reduced mRNA secondary structure near the start codon. Our analysis includes bacteria, archaea, fungi, plants, insects, fishes, birds, and mammals. We find that nearly all species show evidence for reduced mRNA stability near the start codon. The reduction in stability generally increases with increasing genomic GC content. In prokaryotes, the reduction also increases with decreasing optimal growth temperature. Within genomes, there is variation in the stability among genes, and this variation correlates with gene GC content, codon bias, and gene expression level. For birds and mammals, however, we do not find a genome-wide trend of reduced mRNA stability near the start codon. Yet the most GC rich genes in these organisms do show such a signal. We conclude that reduced stability of the mRNA secondary structure near the start codon is a universal feature of all cellular life. We suggest that the origin of this reduction is selection for efficient recognition of the start codon by initiator-tRNA.

Figure 1. The mean and standard error of of each sliding window in E. coli.

Figure 2. The mean of the tenth window vs. the mean of the first window (5′ ).

Each data point represents the entire genome of one organism.

Figure 3. The mean of the first window as a function of the genomic GC content.

Each data point represents one organism.

Figure 4. The mean of the first window as a function of the optimal growth temperature in prokaryotes.

Each data point represents one organism.

Figure 5. Comparison of the mean 5′ between genes with the highest 5% and the lowest 5% GC content within each genome.

Each data point represents one organism.

Figure 6. Comparison of the mean 5′ between genes with the highest 5% and the lowest 5% expression level in E. coli, S. cerevisiae, D. melanogaster, and H. sapiens.