A comparative roadmap of PIWI-interacting RNAs across seven species reveals insights into de novo piRNA-precursor formation in mammals
Parthena Konstantinidou,
Zuzana Loubalova,
Franziska Ahrend,
Aleksandr Friman,
Miguel Vasconcelos Almeida,
Axel Poulet,
Filip Horvat,
Yuejun Wang,
Wolfgang Losert,
Hernan Lorenzi,
Petr Svoboda,
Eric A. Miska,
Josien C. van Wolfswinkel,
Astrid D. Haase
Affiliations
Parthena Konstantinidou
National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
Zuzana Loubalova
National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
Franziska Ahrend
National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA; Oak Ridge Institute for Science and Education, US Department of Energy, Oak Ridge, TN, USA
Aleksandr Friman
National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA; Biophysics Graduate Program, Institute for Physical Science and Technology, University of Maryland, College Park, MD 20742, USA; Institute for Physical Science and Technology, University of Maryland, College Park, MD 20742, USA; Department of Physics, University of Maryland, College Park, MD 20742, USA
Miguel Vasconcelos Almeida
Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, UK; Wellcome/CRUK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK
Axel Poulet
Department of Molecular Cellular and Developmental Biology, Yale University, New Haven, CT 06511, USA; Yale Stem Cell Center, Yale School of Medicine, New Haven, CT 06511, USA; Center for RNA Science and Medicine, Yale School of Medicine, New Haven, CT 06511, USA
Filip Horvat
Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic; Bioinformatics Group, Division of Molecular Biology, Department of Biology, Faculty of Science, University of Zagreb, 10000 Zagreb, Croatia
Yuejun Wang
National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA; Oak Ridge Institute for Science and Education, US Department of Energy, Oak Ridge, TN, USA; TriLab Bioinformatics Group, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Wolfgang Losert
Institute for Physical Science and Technology, University of Maryland, College Park, MD 20742, USA; Department of Physics, University of Maryland, College Park, MD 20742, USA
Hernan Lorenzi
National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA; TriLab Bioinformatics Group, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Petr Svoboda
Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic
Eric A. Miska
Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, UK; Wellcome/CRUK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK
Josien C. van Wolfswinkel
Department of Molecular Cellular and Developmental Biology, Yale University, New Haven, CT 06511, USA; Yale Stem Cell Center, Yale School of Medicine, New Haven, CT 06511, USA; Center for RNA Science and Medicine, Yale School of Medicine, New Haven, CT 06511, USA
Astrid D. Haase
National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA; Corresponding author
Summary: 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.
