A comparative roadmap of PIWI-interacting RNAs across seven species reveals insights into de novo piRNA-precursor formation in mammals
Παρθένα Κωνσταντινίδου, Zuzana Loubalová, Franziska Ahrend, Aleksandr Friman, Miguel Vasconcelos Almeida, Axel Poulet, Filip Horvat, Yuejun Wang, Wolfgang Losert, Hernán Lorenzi, Petr Svoboda, Eric A. Miska, Josien C. van Wolfswinkel, Astrid D. Haase
Abstract
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.