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

Abstract Background 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. Methods 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-Denovo and REDItools2. Results REDItools1, the Denovo 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 early ring stages of the parasites, gradually increasing and then decreasing leading up to the 40-hour mature 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 ring stages of the parasites, gradually decreasing in the later stages. The expression of other RNA editing-related factors was similar in all developmental stages. Pathways associated with RNA editing were found to be downregulated at the 40 h stage, including RNA binding, nucleic acid binding, and catalytic activity acting on RNA pathways. These findings suggest the presence of robust RNA editing machinery in Plasmodium, facilitating rapid base conversions within a short timeframe. Conclusion Our findings will be helpful in identifying the RNA editing machinery, which could serve as a potential tool for antimalarial drug discovery and malaria control in the future.