Dynamic shifts in isomiR profiles during parasite maturation of Fasciola hepatica

We investigated the isomiR profiles of the parasitic worm Fasciola hepatica across three developmental stages: newly excysted juveniles (NEJ), juveniles (JUV), and adults. Our analysis revealed a distinct shift in isomiR distribution during maturation, with NEJs exhibiting a higher abundance and diversity of isomiRs compared to later stages. Notably, isomiRs were often the dominant miRNA form in NEJs, whereas a transition to canonical miRNAs occurred as the parasite matured. This temporal variation suggests that isomiR expression may be linked to the parasite’s life cycle. We observed that truncated isomiRs were more prevalent, with uracil additions at the 3’end and adenosine at the 5’ end being most common. At least 10% of the miRNA population consisted of 5’ end isomiRs, which have the potential to redirect target interactions towards metabolic and developmental pathways. Furthermore, we show that the cleavage sites in F. hepatica primary miRNAs are similar to those found in mammalian cells, and Dicer-mediated cleavage appears to play a significant role in isomiR generation. We believe that the diversification of miRNA sequences through isomiR production is an evolutionary adaptation that enhances the parasite’s ability to tune gene expression during infection and development. This regulatory plasticity may facilitate successful infection and long-term persistence within diverse mammalian hosts. Understanding the roles of isomiRs in parasitic worms could provide new insights into parasite biology and identify potential targets for controlling parasitic infections.