1. Biochemistry and Chemical Biology
  2. Cell Biology

Plasmodium falciparum translational machinery condones polyadenosine repeats

  1. Slavica Pavlovic Djuranovic  Is a corresponding author
  2. Jessey Erath
  3. Ryan J Andrews
  4. Peter O Bayguinov
  5. Joyce J Chung
  6. Douglas L Chalker
  7. James AJ Fitzpatrick
  8. Walter N Moss
  9. Pawel Szczesny  Is a corresponding author
  10. Sergej Djuranovic  Is a corresponding author
  1. Washington University School of Medicine, United States
  2. Iowa State University, United States
  3. Washington University in St Louis, United States
  4. Institute of Biochemistry and Biophysics Polish Academy of Sciences, Poland
https://doi.org/10.7554/eLife.57799
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  1. Slavica Pavlovic Djuranovic
  2. Jessey Erath
  3. Ryan J Andrews
  4. Peter O Bayguinov
  5. Joyce J Chung
  6. Douglas L Chalker
  7. James AJ Fitzpatrick
  8. Walter N Moss
  9. Pawel Szczesny
  10. Sergej Djuranovic
(2020)
Plasmodium falciparum translational machinery condones polyadenosine repeats
eLife 9:e57799.
https://doi.org/10.7554/eLife.57799
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Abstract

Plasmodium falciparum is causative agent of human malaria. Sixty percent of mRNAs from its extremely AT-rich (81%) genome harbor long polyadenosine (polyA) runs within their ORFs, distinguishing the parasite from its hosts and other sequenced organisms. Recent studies indicate polyA runs cause ribosome stalling and frameshifting, triggering mRNA surveillance pathways and attenuating protein synthesis. Here, we show that the P. falciparum is an exception to this rule. We demonstrate that both endogenous genes and reporter sequences containing long polyA runs are efficiently and accurately translated in P. falciparum cells. We show that polyA runs do not elicit any response from No Go Decay (NGD) or result in the production of frameshifted proteins. This is in stark contrast to what we observe in human cells or T. thermophile, an organism with similar AT-content. Finally, using stalling reporters we show that Plasmodium cells evolved not to have a fully functional NGD pathway.

Data availability

All data generated or analysed during this study are included in the manuscript, supporting files or referenced. Source data files have been referenced for Figures 1, 3 and 5, as well as for supplementary figures.

The following previously published data sets were used

Article and author information

Author details

  1. Slavica Pavlovic Djuranovic

    Department of Cell Biology and Physiology, Washington University School of Medicine, Saint Louis, United States
    For correspondence
    spavlov@wustl.edu
    Competing interests
    The authors declare that no competing interests exist.

  2. Jessey Erath

    Department of Cell Biology and Physiology, Washington University School of Medicine, Saint Louis, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Ryan J Andrews

    Roy J Carver Department of Biochemistry, Biophysics, and Molecular Biology, Iowa State University, Ames, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0275-0019

  4. Peter O Bayguinov

    Washington University Center for Cellular Imaging, Washington University School of Medicine, Saint Louis, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Joyce J Chung

    Biology, Washington University in St Louis, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Douglas L Chalker

    Biology, Washington University in St Louis, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0285-3344

  7. James AJ Fitzpatrick

    Department of Neuroscience, Washington University School of Medicine, Saint Louis, United States
    Competing interests
    The authors declare that no competing interests exist.

  8. Walter N Moss

    Roy J Carver Department of Biochemistry, Biophysics, and Molecular Biology, Iowa State University, Ames, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6419-5570

  9. Pawel Szczesny

    Department of Bioinformatics, Institute of Biochemistry and Biophysics Polish Academy of Sciences, Warsaw, Poland
    For correspondence
    szczesny.pawel@gmail.com
    Competing interests
    The authors declare that no competing interests exist.

  10. Sergej Djuranovic

    Department of Cell Biology and Physiology, Washington University School of Medicine, Saint Louis, United States
    For correspondence
    sergej.djuranovic@wustl.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9417-0822

Funding

National Institute of General Medical Sciences (GM112824)

  • Sergej Djuranovic

Washington University in St. Louis (CDI-CORE-2015-505)

  • James AJ Fitzpatrick

National Science Foundation (MCB 1412336)

  • Douglas L Chalker

National Institute of General Medical Sciences (GM112877)

  • Walter N Moss

National Institute of General Medical Sciences (GM007067)

  • Jessey Erath

Washington University in St. Louis (CDI-CORE-2019-813)

  • James AJ Fitzpatrick

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2020, Pavlovic Djuranovic et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Slavica Pavlovic Djuranovic
  2. Jessey Erath
  3. Ryan J Andrews
  4. Peter O Bayguinov
  5. Joyce J Chung
  6. Douglas L Chalker
  7. James AJ Fitzpatrick
  8. Walter N Moss
  9. Pawel Szczesny
  10. Sergej Djuranovic
(2020)
Plasmodium falciparum translational machinery condones polyadenosine repeats
eLife 9:e57799.
https://doi.org/10.7554/eLife.57799

Share this article

https://doi.org/10.7554/eLife.57799

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