Alternative splicing factor is master regulator of sexual development in Plasmodium falciparum

Plasmodium falciparum, the apicomplexan parasite responsible for human malaria has a complex life cycle, during which it undergoes significant biological changes to adapt to different hosts and changing environments. It maintains this complex life cycle with relatively small number of genes. Alternative splicing (AS) is an important post-transcriptional mechanism that enables eukaryotic organisms to expand their protein repertoire out of relatively small number of genes. Ser/Arg-rich (SR) proteins are major regulators of AS in Plasmodium spp. PfSR1 a bona fide SR protein was previously found to not only regulate AS but also steady-state levels of mRNAs. It was found to interact with proteins linked to various processes of RNA metabolism in a stage-dependent manner which included chromatin remodeling, transcription, splicing and translation. Intriguingly, PfSR1 was also previously shown to interact with gametocyte specific genes regulating their steady state transcription levels. In this study, we show that parasite proliferation is significantly decreased upon PfSR1 knockdown in a transgenic line that can produce gametocytes compared to a line that cannot commit to sexual differentiation. This growth delay was found to be due to significant increase in parasites committing to sexual differentiation upon PfSR1 knock down suggesting that PfSR1 plays a regulatory role in sexual commitment of these parasites. The observation was supported by an RNA seq analysis for PfSR1 KD that showed differential upregulation of sexual commitment and gametocyte-specific genes. Further phenotypic and molecular assays will help us understand the functional role of PfSR1 during sexual commitment and throughout gametocytogenesis.