Reading the epitranscriptome of the human malaria parasite

Epigenetic machinery has emerged as a central player in gene regulation and chromatin organization in Plasmodium spp. Epigenetic modifications on histones and their role in antigenic variation in P. falciparum are widely studied. Recent discoveries on nucleic acid methylome are exciting and provide a new dimension to the apicomplexan protozoan parasite's gene regulatory process. Reports have confirmed that N6-methyl adenosine (m6A) methylation plays a crucial role in the translational plasticity of the human malaria parasite during its development in RBC. The YTH domain (YT521-B Homology) protein in P. falciparum binds to m6A epitranscriptome modifications on the mRNA and regulates protein translation. The binding of the PfYTH domain protein to the m6A-modified mRNA is mediated through a binding pocket formed by aromatic amino acids. The P. falciparum genome encodes two members of YTH domain proteins, i.e., YTH1 and YTH2, and both have distinct roles in dictating the epitranscriptome in human malaria parasites. This review highlights recent advancements in the functions and mechanisms of YTH domain protein's role in translational plasticity in the various developmental stages of the parasite.