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Biotech Research


Synonymous Mutations Can Affect Protein Folding And Impair Cellular Fitness

   by Ellen Burns    55
Synonymous Mutations Can Affect Protein Folding And Impair Cellular Fitness

Synonymous codon substitutions affect the mRNA coding sequence, but the encoded amino acid sequence remains unchanged. Therefore, ostensibly these substitutions do not affect the phenotype and are often ignored in the study of human genetic variation. However, a variety of studies have shown that protein levels, translational accuracy, secretory efficiency, final folding structure and post-translational modifications are regulated by multiple mechanisms.

Synonymous codon action has gradually emerged, and the precise mechanism has yet to be discovered. Studies on the interference of synonymous codon substitution on the co-translational folding mechanism often lack in vivo evidence, and usually, rare synonymous codons tend to translate more slowly than ordinary synonymous codons. In addition, rare synonymous codons tend to appear in clusters, many of which are preserved during evolutionary history. The folding rates of many protein secondary and tertiary structures are similar to their synthesis rates, and subtle changes in elongation may also alter the folding mechanism.

Theoretically, synonymous rare codon substitutions reduce translational elongation and can provide more time for the N-terminal portion of the nascent protein to form a stable tertiary structure before the C-terminal portion emerges from the ribosome exit tunnel. Is the extra time good or bad for efficient folding? Cells contain a chaperone network to facilitate protein folding. It is unclear whether altered elongation and co-translational folding mechanisms of synonymous codons interfere with chaperone function.

7th Annual Peptides & Oligonucleotides Congress

   by BiopharmaTrend    214
7th Annual Peptides & Oligonucleotides Congress

With major developments in the peptide field and with more and more peptide and oligonucleotide therapeutics entering clinical trials, the real promise of peptides and oligonucleotides is starting to be realised. Part of our Biologics Series, this event will take you through the key stages of peptide development from peptide discovery through to formulation and delivery, manufacturing and synthesis, as well as oligonucleotide synthesis, chemistry, formulation, as well as therapeutics and manufacturing.