Plasmodium spp. are the single-celled, eukaryotic causative agents of malaria. P. falciparum is one of the most well studied protists as it is one of the deadliest infectious agents in human history. This parasite has a small, relatively well annotated genome consisting of around 5,000 genes. The expression of these genes in the pathogenic stage, the intra-erythrocytic developmental cycle, underlies key mechanisms of pathogenesis.
Plasmodium falciparum is known to contain many mRNA modifications. The N6-methyladenosine (m6A) writer’s core in P. falciparum is related to other known eukaryotic m6A writers, consisting of the WTAP adaptor and orthologs of METTL3 and METTL14. The METTL3 ortholog which is annotated as PfMT-A70, is essential during the intra-erythrocytic developmental cycle, and m6A is likely an important regulator of gene expression at this stage of the parasites’ lifecycle.
Transcriptome-wide studies suggests that m6A deposition on mRNA destabilises those transcripts as a mechanism of repressing their expression. This is likely a crucial layer of regulation for maintaining mRNA homeostasis in the context of P. falciparum, which has one of the lowest proportions of transcription factors to genes among eukaryotes.
This study aims to establish that m6A affects the stability of mRNA by measuring the rate of mRNA decay following inhibition of transcription. We also describe how knockdown of PfMT-A70 affects the proteome.
The relatively small genome of P. falciparum makes transcriptomic and proteomic studies more feasible. As the m6A machinery in P. falciparum is related to that of humans, insights gained this work can be applied to work on human mRNA biology, RNA viruses that infect eukaryotes and mRNA vaccines.