Dynamic Regulation of RNA mA Methylation in the Ribonucleoprotein Complexes in Apicomplexan and Kinetoplastid Parasites.

mA, or N-methyladenosine, is a the most abundant modification of mRNA transcripts. These modifications are known to influence mRNA transcript stability, transcription, translation, alternative splicing and decay, with undoubtedly more functions to be discovered. In this review, we explored the roles of mA modifications in two groups of protozoan parasites: the apicomplexans, which include Plasmodium and Toxoplasma species, and kinetoplastids, which include Trypanosoma and Leishmania species. We also compared the key players of mA epitranscriptomic machinery in creating, interpreting, and removing mA modifications between these parasitic protists as well as a discussion of how mA modifications facilitate parasite survival through features specific to apicomplexans and kinetoplastids. Beyond parasite epitranscriptomes, this review compares mA dynamics in host and vector species (humans, flies and mosquitoes), highlighting coevolutionary adaptations. Strikingly, both the parasites and their vectors lack canonical mA demethylases, implying a largely irreversible, streamlined mA landscape fine-tuned for synchronized gene regulation. Overall, a mechanistic understanding is emerging of how mA-modified RNAs and their binding proteins orchestrate RNA processing, translation, and turnover in parasitic protists, revealing an evolutionarily tuned epitranscriptomic system.