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Genetic paradox explained by nonsense

Gene mutations that truncate the encoded protein can trigger the expression of related genes. The discovery of this compensatory response changes how we think about genetic studies in humans and model organisms.
  1. Miles F. Wilkinson

    1. Miles F. Wilkinson is in the Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, California 92093, USA.

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Conventional wisdom holds that modifying a gene to make the encoded protein inactive — ‘knocking out’ the gene — will have more severe effects than merely reducing the gene’s expression level. However, there are many cases in which the opposite occurs. In fact, the knockout of a gene sometimes has no discernible impact, whereas the reduction of expression (knockdown) of the same gene causes major defects1. Off-target or toxic effects of the reagents used for gene knockdown have sometimes been found to be the culprit2, but not always3, leaving one to wonder what else could be responsible. Writing in Nature, El-Brolosy et al.4 and Ma et al.5 provide an intriguing solution to this paradox.

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Nature 568, 179-180 (2019)

doi: https://doi.org/10.1038/d41586-019-00823-5

References

  1. El-Brolosy, M. A. & Stainier, D. Y. R. PLoS Genet. 13, e1006780 (2017).

    Article  Google Scholar 

  2. Kok, F. O. et al. Dev. Cell 32, 97–108 (2015).

    Google Scholar 

  3. Rossi, A. et al. Nature 524, 230–233 (2015).

    Article  PubMed  Google Scholar 

  4. El-Brolosy, M. A. et al. Nature 568, 193–197 (2019).

    Article  Google Scholar 

  5. Ma, Z. et al. Nature 568, 259–263 (2019).

    Article  Google Scholar 

  6. Zhu, P. et al. J. Genet. Genom. 44, 553–556 (2017).

    Article  Google Scholar 

  7. Popp, M. W.-L. & Maquat, L. E. Annu. Rev. Genet. 47, 139–165 (2013).

    Article  PubMed  Google Scholar 

  8. Howe, F. S., Fischl, H., Murray, S. C. & Mellor, J. BioEssays 39, 1600095 (2016).

    Article  Google Scholar 

  9. Haimovich. G. et al. Cell 153, 1000–1011 (2013).

    Article  PubMed  Google Scholar 

  10. Shum, E. Y. et al. Cell 165, 382–395 (2016).

    Article  PubMed  Google Scholar 

  11. MacArthur, D. G. et al. Science 335, 823–828 (2012).

    Article  PubMed  Google Scholar 

  12. Brooks, P. C. et al. Cell 79, 1157–1164 (1994).

    Article  PubMed  Google Scholar 

  13. Bader, B. L., Rayburn, H., Crowley, D. & Hynes, R. O. Cell 95, 507–519 (1998).

    Article  Google Scholar 

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