Translation efficiency is determined by both codon bias and folding energy

Area of Science:

• Molecular Biology
• Genomics
• Bioinformatics

Background:

• Synonymous mutations can alter protein levels without changing the protein sequence.
• The mechanisms driving this phenomenon, such as codon bias and mRNA folding, are debated.

Purpose of the Study:

• To investigate the genome-wide determinants of translation efficiency in Escherichia coli and Saccharomyces cerevisiae.
• To clarify the relative importance of codon bias versus mRNA folding energy in regulating translation efficiency.

Main Methods:

• Genome-scale analysis of transcriptomes from E. coli and S. cerevisiae.
• Correlation analysis between codon bias, mRNA folding energy, and translation efficiency.
• Examination of ribosomal density profiles and selection pressures on mRNA folding at gene beginnings.

Main Results:

• A significant association was found between codon bias and translation efficiency across endogenous genes.
• No direct association was observed between folding energy and translation efficiency, but it modulates the codon bias effect.
• Lower folding energies correlate with decreased translation efficiency by slowing ribosome movement.
• Selection pressures favor reduced folding energy at the start of genes.

Conclusions:

• Codon bias is a key determinant of translation efficiency in E. coli and S. cerevisiae.
• mRNA folding energy influences translation efficiency globally, not just at translation initiation, and its effects are intertwined with codon bias.
• Previous studies may have overlooked the global role of folding energy due to its complex interaction with expression levels.