Nonoptimal Codon Usage Is Critical for Protein Structure and Function of the Master General Amino Acid Control Regulator CPC-1

• DOI: 10.1128/mbio.02605-20
• Publication Date: 2020-10-12T13:27:23Z
• Authors: Xueliang Lyu; Yi Liu
• Keywords: 2. Zero hunger; Protein Folding; codon usage; Neurospora crassa; Saccharomyces cerevisiae; Microbiology; QR1-502; Fungal Proteins; Neurospora; CPC-1; cotranslational protein folding; cross-pathway control; Gene Expression Regulation, Fungal; Protein Biosynthesis; GCN4; Amino Acids; Codon Usage; Research Article

The general amino acid control response is critical for adaptation of organisms to amino acid starvation conditions. The preference to use certain synonymous codons is a universal feature of all genomes. Synonymous codon changes were previously thought to be silent mutations. In this study, we showed that the Neurospora cpc-1 gene has an unusual codon usage profile compared to other genes in the genome. We found that codon optimization of the cpc-1 gene without changing its amino acid sequence resulted in elevated CPC-1 expression, an altered protein degradation rate, and impaired protein functions due to changes in protein structure. Together, these results reveal the critical role of synonymous codon usage in regulation of CPC-1 expression and function and establish a genetic example of the importance of codon usage in protein structure.