Expression of Human nPTB Is Limited by Extreme Suboptimal Codon Content “Humanizing” a Human ORF
2008

How Codon Content Affects Protein Expression in Humans

publication Evidence: moderate

Author Information

Author(s): Fiona Robinson, Richard J. Jackson, Christopher W. J. Smith

Primary Institution: Department of Biochemistry, University of Cambridge

Hypothesis

Does the codon content of human proteins affect their expression levels in human cells?

Conclusion

The study shows that suboptimal codon content significantly limits the expression of the nPTB protein in human cells.

Supporting Evidence

  • nPTB was expressed at only 1-3% the level of PTB despite similar mRNA levels.
  • Optimization of nPTB's codon content allowed for efficient translation comparable to PTB.
  • Both nPTB and ROD1 were shown to act as splicing repressors when expressed at adequate levels.

Takeaway

This study found that some proteins don't get made as much in our cells because their building instructions (codons) are not the best fit for our cell machinery.

Methodology

The researchers compared the expression levels of human PTB and its paralogs nPTB and ROD1 in various cell lines, analyzing the impact of codon optimization on protein expression.

Limitations

The study primarily focuses on transient transfection in cell lines, which may not fully represent in vivo conditions.

Digital Object Identifier (DOI)

10.1371/journal.pone.0001801

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