2026/05/01 by Isaac Martínez-Ugalde, Kyriaki Neophytou, Yenetzi Villagrana-Pacheco +9 · 1 voice
Agricultural and Biological Sciences · Immunology and Microbiology · Medicine · #Chromosomal and Genetic Variations #Parasites and Host Interactions #Viral Infections and Immunology Research
paper · doi:10.1093/gbe/evag117
openalex created_date 2025/10/10 · openalex publication_date 2026/05/01 · openalex updated_date 2026/07/31
Safeguarding the genome from non-self-elements is essential for development, reproduction, and aging. One of the major threats to genomic integrity is transposable elements (TEs), which can be post-transcriptionally silenced through small RNAs (sRNAs) and argonaute proteins. Recent work suggests TE-derived sRNAs may also act as virulence factors in host-pathogen interactions. During infection, the intestinal parasite Heligmosomoides bakeri secretes a single argonaute protein (exWAGO) and a wide variety of TE-derived sRNAs. Although exWAGO is highly expressed, conserved, and secreted by parasitic nematodes, its function and sRNA guide preference remain unclear. Using comparative transcriptomics of the sRNAs bound to exWAGO within parasites of rodents, livestock, and humans, and its orthologs in C. elegans, we found that exWAGO is capable of loading sRNAs produced from all classes of TEs in addition to some protein-coding and noncoding transcripts. However, our results suggest that the ancestral endogenous function of exWAGO was likely linked to LTR retrotransposon regulation. To understand how this relates to potential extracellular functions of exWAGO, we also examined the sRNAs bound to exWAGO secreted by H. bakeri in both vesicular and nonvesicular forms. Extracellular exWAGO preferentially loads sRNA guides derived from nonautonomous and fragmented LTRs, suggesting the existence of adaptable reservoirs of regulatory sRNAs with potential roles in cross-species RNA communication. Together, our results show that exWAGO is part of an evolutionarily conserved pathway for LTR retrotransposon regulation, while preferentially utilizing degenerated elements as sources of secreted sRNAs.