Adjacent Codons Act in Concert to Modulate Translation Efficiency in Yeast

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• Translation elongation efficiency was previously considered an additive function of individual codon decoding.
• The role of adjacent codons in modulating translation speed and accuracy remained largely unexplored.

Purpose of the Study:

• To investigate the impact of adjacent codon pairs on translation elongation efficiency.
• To identify specific codon pairs that influence protein expression levels.

Main Methods:

• Utilized a high-throughput screening approach in Saccharomyces cerevisiae.
• Randomized three adjacent codons in over 35,000 Green Fluorescent Protein (GFP) variants to assess expression levels.
• Analyzed ribosome profiling data from endogenous genes.

Main Results:

• Identified 17 pairs of adjacent codons associated with significantly reduced expression.
• Demonstrated that the order of codons within a pair is often critical for the observed inhibition.
• Showed that increased transfer RNA (tRNA) levels or the introduction of non-native tRNAs can restore GFP expression, indicating the effect occurs during translation.
• Confirmed the inhibitory effect of specific adjacent codon pairs in endogenous genes.

Conclusions:

• Adjacent codon pairs, not just individual codons, play a crucial role in modulating translation efficiency.
• The interplay between tRNAs interacting with adjacent codons in the ribosome influences protein synthesis.
• These findings necessitate a re-evaluation of codon choice impact on gene function and protein production.