Single-target high-throughput transcription analyses reveal high levels of alternative splicing present in the FPPS/GGPPS from Plasmodium falciparum

Malaria is a tropical disease with significant morbidity and mortality. A better understanding of the metabolism of its most important etiological agent, Plasmodium falciparum, is paramount to the development of better treatment and other mitigation measures. Farnesyldiphosphate synthase/geranylgeranyldiphosphate synthase (FPPS/GGPPS) is a key enzyme in the synthesis of isoprenic chains present in many essential structures. In P. falciparum, as well as a handful of other organisms, FPPS/GGPPS has been shown to be a bifunctional enzyme. By genetic tagging and microscopy, we observed a changing localization of FPPS/GGPPS in blood stage parasites. Given the great importance of alternative splicing and other transcriptional phenomena in gene regulation and the generation of protein diversity, we have investigated the processing of the FPPS/GGPPS transcript in P. falciparum by high-throughput sequencing methods in four time-points along the intraerythrocytic cycle of P. falciparum. We have identified levels of transcript diversity an order of magnitude higher than previously observed in this organism, as well as a few stage-specific splicing events. Our data suggest that alternative splicing in P. falciparum is an important feature for gene regulation and the generation of protein diversity.