Genome-wide detection of conserved stage-specific RNA editing events for nuclear genes in the Plasmodium falciparum 3D7 malaria parasite.

RNA editing is an important post-transcriptional modification of RNA. While transcriptional variation is a well-studied phenomenon in Plasmodium, post-transcriptional modifications, such as RNA editing, have not received as much scrutiny. We detected genome-wide RNA editing in a developmental stage-specific manner at 16 h, 24 h, 32 h, and 40 h of tightly synchronized P. falciparum 3D7 by using the RNA editing computational approaches REDItools1-De novo and REDItools2. REDItools1-De novo approach revealed extensive A-to-G, G-to-A, and T-to-C type variations in almost all stages. With the REDItools2 approach and screening, almost all editing events were observed in time-specific parasitic stages. G-to-A and C-to-T events were found at much higher levels. We observed significant differences in stage-specific RNA editing at 8-h intervals. RNA editing was observed at the ring 16 h stages of the parasites, reached a peak during the 32 h trophozoite stage, and declined at the 40 h schizont stage. Adenosine deaminase expression did not correlate with the editing level in a time-dependent manner. However, the expression of cytidine deaminase was found to be higher in the 16 h of the parasites, decreased as the parasite matured. Pathways associated with RNA editing- including RNA binding, nucleic acid binding and catalytic activity acting on RNA pathways were found to be downregulated at the 40 h stage. These findings suggest the presence of robust RNA editing machinery in Plasmodium, facilitating rapid base conversions within a short timeframe. Our results provide a foundation for identifying the Plasmodium RNA editing factors and their effect in the future research.