Plasmodium falciparum translational machinery condones polyadenosine repeats
- Washington University School of Medicine, United States
- Iowa State University, United States
- Washington University in St Louis, United States
- Institute of Biochemistry and Biophysics Polish Academy of Sciences, Poland
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.
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Ribosome Profiling in P. falciparum asexual blood stagesNCBI Gene Expression Omnibus, GSE58402.
Article and author information
Author details
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.
Reviewing Editor
- Nahum Sonenberg, McGill University, Canada
Publication history
- Received: April 16, 2020
- Accepted: May 28, 2020
- Accepted Manuscript published: May 29, 2020 (version 1)
- Version of Record published: June 15, 2020 (version 2)
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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Plasmodium falciparum translational machinery condones polyadenosine repeats
eLife 9:e57799.
https://doi.org/10.7554/eLife.57799
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