Nonoptimal codon usage influences protein structure in intrinsically disordered regions.

Area of Science:

• Genetics
• Molecular Biology
• Biophysics

Background:

• Synonymous codon frequencies vary across genomes, influencing translation and protein folding.
• The interplay between codon usage, protein structure, and in vivo folding in eukaryotes remains largely unexplored.

Purpose of the Study:

• To investigate the relationship between codon usage bias and protein secondary structures in Neurospora.
• To determine the in vivo functional significance of codon usage in eukaryotic protein folding.

Main Methods:

• Analyzed codon usage bias in the filamentous fungus Neurospora.
• Correlated codon choices with predicted protein secondary structures genome-wide.
• Performed structure-based codon manipulation in the Neurospora circadian clock gene frequency (frq).

Main Results:

• Identified a strong codon usage bias in Neurospora with genome-wide correlations between codon bias and protein structure.
• Found non-optimal codons enriched in intrinsically disordered regions and optimal codons in structured domains.
• Demonstrated that optimizing codons in disordered regions of FRQ impairs circadian clock function and alters protein structure.

Conclusions:

• Codon choices and protein structures co-evolve to ensure proper protein folding in eukaryotes.
• Codon usage bias plays a functional role in regulating protein structure and biological processes in vivo.
• The observed correlations between codon usage and protein disorder are conserved across eukaryotes.