PT  - JOURNAL ARTICLE
AU  - Slavica Pavlovic Djuranovic
AU  - Jessey Erath
AU  - Ryan J Andrews
AU  - Peter O Bayguinov
AU  - Joyce J Chung
AU  - Douglas L Chalker
AU  - James AJ Fitzpatrick
AU  - Walter N Moss
AU  - Pawel Szczesny
AU  - Sergej Djuranovic
TI  - PolyA tracks and poly-lysine repeats are the Achilles heel of &lt;em&gt;Plasmodium falciparum&lt;/em&gt;
AID  - 10.1101/420109
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 420109
4099  - http://biorxiv.org/content/early/2018/09/18/420109.short
4100  - http://biorxiv.org/content/early/2018/09/18/420109.full
AB  - Plasmodium falciparum, the causative agent of human malaria, is an apicomplexan parasite with a complex, multi-host life cycle. Sixty percent of transcripts from its extreme AT-rich (81%) genome possess coding polyadenosine (polyA) runs, distinguishing the parasite from its hosts and other sequenced organisms. Recent studies indicate that transcripts with polyA runs encoding poly-lysine are hot spots for ribosome stalling and frameshifting, eliciting mRNA surveillance pathways and attenuating protein synthesis in the majority of prokaryotic and eukaryotic organisms. Here, we show that the P. falciparum translational machinery is paradigm-breaking. Using bioinformatic and biochemical approaches, we demonstrate that both endogenous genes and reporter sequences containing long polyA runs are efficiently and accurately transcribed and translated in P. falciparum cells. Translation of polyA tracks in the parasite does not elicit any response from mRNA surveillance pathways usually seen in host human cells or organisms with similar AT content. The translation efficiency and accuracy of the parasite protein synthesis machinery reveals a unique role of ribosomes in the evolution and adaptation of P. falciparum to an AU-rich transcriptome and polybasic amino sequences. Finally, we show that the ability of P. falciparum to synthesize long poly-lysine repeats has given this parasite a unique protein exportome and an advantage in infectivity that can be suppressed by addition of exogenous poly-basic polymers.