Our analyses of polyA tracks in eukaryotic genomes (Habich et al., 2016) led us to our research on the malaria-causing parasite, P. falciparum, where polyA tracks are found in more than 60% of coding mRNAs. Plasmodium falciparum has a highly imbalanced genomic composition with AT content over 80%. Despite the knowledge of the whole Plasmodium genome, designs for effective vaccines against it have failed to provide substantial protection. Our findings show that runs of coding polyadenosine nucleotides in genes, so-called polyA tracks, act as negative gene expression regulators in most tested organisms (Arthur et al., 2015, 2017, 2018, Koutmou et al., 2015, Habich et al., 2016). Attenuation is facilitated through ribosomal stalling and frameshifting, and governed by mRNA and protein quality control mechanisms. Plasmodium species are an intriguing exception to this rule since polyA tracks are efficiently expressed in P. falciparum (Pavlovic Djuranovic et al., 2019). We seek to understand why and how Plasmodium protein synthesis machinery is able to effectively translate polyA track transcripts. By understanding this process, we will begin to understand the fundamental differences in translation of the transcriptome between Plasmodium and other organisms. Our studies of P. falciparum protein synthesis and mRNA surveillance mechanisms as well as our data on polyA tracks have the potential to determine new malarial drug targets. To achieve these goals, we are combining biochemical, biophysical and molecular biology approaches to probe why and how the translation apparatus and quality control mechanisms in Plasmodium differ from other Eukaryotes. Our data from P. falciparum strongly indicates that efficient protein synthesis from the AT-rich genome is enabled by novelties in ribosome structure, attenuation of mRNA surveillance and mRNA degradation mechanisms, as well as an increase in the number of translation-associated RNA helicases in parasites. Using genome engineering techniques, we are now able to test the contribution of Plasmodium ribosomes, mRNA surveillance components and RNA helicases in the evolution of unusually high AU-rich transcriptome. As such, our studies on alterations of P. falciparum protein synthesis move research into a novel and exciting direction, and we hope they will provide further clues for the medical treatment of malaria.
