Non-parasite genome encoded virus-like RNAs reprogram the pathogenicity of human blood flukes.

Non-parasite genome encoded RNAs (ngRNAs) are often overlooked in their roles, especially their functions in shaping the biology of organisms. Here we show four non-parasite genome encoded virus-like RNAs that present in Schistosoma japonicum, a human blood fluke responsible for significant morbidity and mortality. These ngRNAs are predominantly localized in the germ cells that play crucial roles in oogenesis and egg production, pivotal processes contributing to host pathology. The ngRNA encode RNA-dependent RNA polymerase (RdRp) that synthesize complementary RNA strands, governing embryo viability and egg production. Notably, similar virus-like ngRNAs are also found in the planarian Dugesia japonica, where RdRp sustains worm survival. In this work, we integrate metatranscriptomics, single-cell RNA sequencing, RNA interference and various molecular methods to comprehensively identify ngRNAs and then characterize their functions. We further demonstrate the mechanism by which ngRNAs shape critical biological traits in parasitic helminths, providing novel insights into potential therapeutic targets for schistosomiasis control and advancing our understanding of ngRNA functions in certain organisms.