Plasmodium falciparum translational machinery condones polyadenosine repeats
Open Access
- 29 May 2020
- journal article
- research article
- Published by eLife Sciences Publications, Ltd in eLife
Abstract
Plasmodium falciparum is a 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 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. thermophila, an organism with similar AT-content. Finally, using stalling reporters we show that Plasmodium cells evolved not to have a fully functional NGD pathway.Keywords
Funding Information
- National Institute of General Medical Sciences (R01 GM112824)
- National Science Foundation (MCB 1412336)
- National Institute of General Medical Sciences (R00 GM112877)
- National Institute of General Medical Sciences (T32 GM007067)
- St. Louis Children’s Hospital (CDI-CORE-2015-505)
- St. Louis Children’s Hospital (CDI-CORE-2019-813)
- Washington University School of Medicine in St. Louis
- Foundation for Barnes-Jewish Hospital (3770)
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