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Expanding the genetic code of Drosophila melanogaster

Nature Chemical Biology volume 8, pages 748–750 (2012)Cite this article

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Abstract

Genetic code expansion for unnatural amino acid mutagenesis has, until recently, been limited to cell culture. We demonstrate the site-specific incorporation of unnatural amino acids into proteins in Drosophila melanogaster at different developmental stages, in specific tissues and in a subset of cells within a tissue. This approach provides a foundation for probing and controlling processes in this established metazoan model organism with a new level of molecular precision.

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Figure 1: Site-specific incorporation and labeling of unnatural amino acids in D. melanogaster Dmel cells using an orthogonal MmPylRS/tRNACUA pair.
Figure 2: Site-specific incorporation of unnatural amino acids in D. melanogaster embryos.
Figure 3: Tissue-specific and subtissue-specific incorporation of unnatural amino acids in D. melanogaster ovaries.

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References

  1. Davis, L. & Chin, J.W. Nat. Rev. Mol. Cell Biol. 13, 168–182 (2012).

    Article  CAS  Google Scholar 

  2. Liu, C.C. & Schultz, P.G. Annu. Rev. Biochem. 79, 413–444 (2010).

    Article  CAS  Google Scholar 

  3. Gautier, A., Deiters, A. & Chin, J.W. J. Am. Chem. Soc. 133, 2124–2127 (2011).

    Article  CAS  Google Scholar 

  4. Gautier, A. et al. J. Am. Chem. Soc. 132, 4086–4088 (2010).

    Article  CAS  Google Scholar 

  5. Lemke, E.A., Summerer, D., Geierstanger, B.H., Brittain, S.M. & Schultz, P.G. Nat. Chem. Biol. 3, 769–772 (2007).

    Article  CAS  Google Scholar 

  6. Rubin, G.M. & Lewis, E.B. Science 287, 2216–2218 (2000).

    Article  CAS  Google Scholar 

  7. Adams, M.D. et al. Science 287, 2185–2195 (2000).

    Article  Google Scholar 

  8. Brand, A.H. & Perrimon, N. Development 118, 401–415 (1993).

    CAS  Google Scholar 

  9. Rubin, G.M. & Spradling, A.C. Science 218, 348–353 (1982).

    Article  CAS  Google Scholar 

  10. Laski, F.A., Ganguly, S. & Sharp, P.A. Proc. Natl. Acad. Sci. USA 86, 6696–6698 (1989).

    Article  CAS  Google Scholar 

  11. Garza, D., Medhora, M.M. & Hartl, D.L. Genetics 126, 625–637 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Washburn, T. & O'Tousa, J.E. Genetics 130, 585–595 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Lang, K. et al. Nat. Chem. 4, 298–304 (2012).

    Article  CAS  Google Scholar 

  14. Nguyen, D.P. et al. J. Am. Chem. Soc. 131, 8720–8721 (2009).

    Article  CAS  Google Scholar 

  15. Nguyen, D.P., Garcia Alai, M.M., Kapadnis, P.B., Neumann, H. & Chin, J.W. J. Am. Chem. Soc. 131, 14194–14195 (2009).

    Article  CAS  Google Scholar 

  16. Neumann, H., Peak-Chew, S.Y. & Chin, J.W. Nat. Chem. Biol. 4, 232–234 (2008).

    Article  CAS  Google Scholar 

  17. Nguyen, D.P. Unnatural Amino Acid Incorporation via the Orthogonal Pyrrolysyl-tRNA Synthetase–tRNACUA Pair. PhD thesis, Univ. Cambridge (2012).

  18. Chen, P.R. et al. Angew. Chem. Int. Edn. Engl. 48, 4052–4055 (2009).

    Article  CAS  Google Scholar 

  19. Mukai, T. et al. Biochem. Biophys. Res. Commun. 371, 818–822 (2008).

    Article  CAS  Google Scholar 

  20. Greiss, S. & Chin, J.W. J. Am. Chem. Soc. 133, 14196–14199 (2011).

    Article  CAS  Google Scholar 

  21. Isogai, Y., Takada, S., Tjian, R. & Keles, S. EMBO J. 26, 79–89 (2007).

    Article  Google Scholar 

  22. Mukai, T., Wakiyama, M., Sakamoto, K. & Yokoyama, S. Protein Sci. 19, 440–448 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Bunch, T.A., Grinblat, Y. & Goldstein, L.S. Nucleic Acids Res. 16, 1043–1061 (1988).

    Article  CAS  Google Scholar 

  24. Van Doren, M., Williamson, A.L. & Lehmann, R. Curr. Biol. 8, 243–246 (1998).

    Article  CAS  Google Scholar 

  25. Pignoni, F. & Zipursky, S.L. Development 124, 271–278 (1997).

    CAS  PubMed  Google Scholar 

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Acknowledgements

This work was funded by the UK Medical Research Council (MRC) (grants U105181009 and UD99999908) and the Louis-Jeantet Foundation Young Investigator Career Award (both to J.W.C.). We are grateful to S. Bullock (MRC Laboratory of Molecular Biology) for providing initial plasmids and for extensive help and advice with this project; to S. Peak-Chew and M. Skehel in the MRC Laboratory of Molecular Biology Mass Spectrometry Facility for MS; S. Brunner for assistance with statistical analysis; and J. Schmitz and R. Pisa for experimental assistance.

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Author notes

  1. Ambra Bianco, Fiona M Townsley and Sebastian Greiss: These authors contributed equally to this work.

Authors and Affiliations

  1. Medical Research Council Laboratory of Molecular Biology, Cambridge, UK

    Ambra Bianco, Fiona M Townsley, Sebastian Greiss, Kathrin Lang & Jason W Chin

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  1. Ambra Bianco
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  2. Fiona M Townsley
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Contributions

A.B., F.M.T. and S.G. designed and performed experiments. K.L. provided compounds. A.B. and J.W.C. wrote the paper with input from all authors.

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Correspondence to Jason W Chin.

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The authors declare no competing financial interests.

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Bianco, A., Townsley, F., Greiss, S. et al. Expanding the genetic code of Drosophila melanogaster. Nat Chem Biol 8, 748–750 (2012). https://doi.org/10.1038/nchembio.1043

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