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Protein yield is tunable by synonymous codon changes of translation initiation sites

View ORCID ProfileBikash K. Bhandari, View ORCID ProfileChun Shen Lim, Daniela M. Remus, Augustine Chen, View ORCID ProfileCraig van Dolleweerd, View ORCID ProfilePaul P. Gardner
doi: https://doi.org/10.1101/726752
Bikash K. Bhandari
1Department of Biochemistry, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand
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Chun Shen Lim
1Department of Biochemistry, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand
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Daniela M. Remus
3Callaghan Innovation Protein Science and Engineering, University of Canterbury, Christchurch, New Zealand
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Augustine Chen
1Department of Biochemistry, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand
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Craig van Dolleweerd
3Callaghan Innovation Protein Science and Engineering, University of Canterbury, Christchurch, New Zealand
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Paul P. Gardner
1Department of Biochemistry, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand
2Biomolecular Interaction Centre, University of Canterbury, Christchurch, New Zealand
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  • For correspondence: paul.gardner@otago.ac.nz
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ABSTRACT

Recombinant protein production is a key process in generating proteins of interest in the pharmaceutical industry and biomedical research. However, about 50% of recombinant proteins fail to be expressed in a variety of host cells. To address this problem, we modified up to the first nine codons of messenger RNAs with synonymous substitutions and showed that protein levels can be tuned. These modifications alter the ‘accessibility’ of translation initiation sites. We also reveal the dynamics between accessibility, gene expression, and turnovers using a coarse-grained simulation.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Author addresses fixed. Abstract revised.

  • https://tisigner.com/tisigner

  • https://bkb3.github.io/TIsignerExperiment/

  • https://github.com/Gardner-BinfLab/TIsigner_paper_2019

  • https://github.com/Gardner-BinfLab/TISIGNER-ReactJS

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted February 22, 2021.
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Protein yield is tunable by synonymous codon changes of translation initiation sites
Bikash K. Bhandari, Chun Shen Lim, Daniela M. Remus, Augustine Chen, Craig van Dolleweerd, Paul P. Gardner
bioRxiv 726752; doi: https://doi.org/10.1101/726752
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Protein yield is tunable by synonymous codon changes of translation initiation sites
Bikash K. Bhandari, Chun Shen Lim, Daniela M. Remus, Augustine Chen, Craig van Dolleweerd, Paul P. Gardner
bioRxiv 726752; doi: https://doi.org/10.1101/726752

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