Figure 1.

Schematic illustration of the hypothesis that Toxoplasma infection alters miRNA pathway leading to brain carcinogenesis. The miRNA synthesis pathway is mediated by multiple protein complexes that sequentially cleave, export and incorporate miRNA into the silencing machinery. miRNA is transcribed by RNA polymerase II or III and this pri-miRNA is processed by Drosha–DGCR8 (Pasha) complex to pre-miRNA, which is exported from the nucleus by Exportin-5 to the cytoplasm. The RNase Dicer is associated with the double-stranded RNA-binding protein TRBP and the PKR activator PACT processes the pre-miRNA hairpin to 22-nt miRNA duplexes. One strand of mature miRNA is loaded into the RNA-induced silencing complex (RISC) along with Argonaute (Ago2) proteins and it directs RISC to silence target mRNAs through mRNA cleavage or translational repression while the complementary strand is degraded. This pathway is tightly regulated at transcriptional and post transcriptional level. The miRNA stability and post translational modifications are used to modulate the functionality of the miRNAs. Proteins of miRNA processing complexes also play a crucial role in regulating the miRNA processing pathway. We hypothesize that effector molecules released by Toxoplasma into the host cell may interfere with miRNA synthesis and maturation pathway, which in turn modulate host cell survival or death signaling pathways.