A comparative roadmap of PIWI-interacting RNAs across seven species reveals insights into de novo piRNA-precursor formation in mammals

• DOI: 10.1016/j.celrep.2024.114777
• Publication Date: 2024-09-19T13:16:39Z
• Authors: Parthena Konstant...; Zuzana Loubalova; Franziska Ahrend; Aleksandr Friman; Miguel Vasconcelo...; Axel Poulet; Filip Horvat; Yuejun Wang; Wolfgang Losert; Hernan Lorenzi; Petr Svoboda; Eric A. Miska; Josien C. van Wol...; Astrid D. Haase
• Keywords: Piwi-interacting RNA; Argonaute; Small nucleolar RNA; RasiRNA

PIWI-interacting RNAs (piRNAs) play a crucial role in safeguarding genome integrity by silencing mobile genetic elements. From flies to humans, piRNAs originate from long single-stranded precursors encoded by genomic piRNA clusters. How piRNA clusters form to adapt to genomic invaders and evolve to maintain protection remain key outstanding questions. Here, we generate a roadmap of piRNA clusters across seven species that highlights both similarities and variations. In mammals, we identify transcriptional readthrough as a mechanism to generate piRNAs from transposon insertions (piCs) downstream of genes (DoG). Together with the well-known stress-dependent DoG transcripts, our findings suggest a molecular mechanism for the formation of piRNA clusters in response to retroviral invasion. Finally, we identify a class of dynamic piRNA clusters in humans, underscoring unique features of human germ cell biology. Our results advance the understanding of conserved principles and species-specific variations in piRNA biology and provide tools for future studies.