A comparative roadmap of PIWI-interacting RNAs across seven species reveals insights into de novo piRNA-precursor formation in mammals
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.
Authors
- Filip Horvat (ORCID: https://orcid.org/0000-0002-1896-7645)
- Παρθένα Κωνσταντινίδου (ORCID: https://orcid.org/0009-0005-0492-4117)
- Eric A. Miska (ORCID: https://orcid.org/0000-0002-4450-576X)
- Aleksandr Friman (ORCID: https://orcid.org/0000-0002-7968-8455)
- Axel Poulet (ORCID: https://orcid.org/0000-0002-3415-8960)
- Astrid D. Haase (ORCID: https://orcid.org/0000-0003-1120-9013)
- Zuzana Loubalová (ORCID: https://orcid.org/0000-0002-8876-4456)
- Petr Svoboda (ORCID: https://orcid.org/0000-0002-4370-3705)
- Miguel Vasconcelos Almeida (ORCID: https://orcid.org/0000-0002-4816-3111)
- Hernán Lorenzi (ORCID: https://orcid.org/0000-0003-0910-7894)
- Wolfgang Losert (ORCID: https://orcid.org/0000-0002-1792-7860)
- Josien C. van Wolfswinkel (ORCID: https://orcid.org/0000-0003-4221-3218)
- Franziska Ahrend
- Yuejun Wang (ORCID: https://orcid.org/0000-0002-4336-0255)
Institutions
- National Institutes of Health (US)
- The Gurdon Institute (GB)
- Yale University (US)
- National Institute of Diabetes and Digestive and Kidney Diseases (US)
- Institute of Molecular Genetics (RU)
- Czech Academy of Sciences, Institute of Molecular Genetics (CZ)
- University of Maryland, College Park (US)
Publication Details
- Journal
- Cell Reports
- Published
- 2024-09-19
- DOI
- https://doi.org/10.1016/j.celrep.2024.114777
- Citations
- 14
- Primary Topic
- Chromosomal and Genetic Variations
- Type
- article
- Field-Weighted Citation Impact
- 8.39
Funders
- Vallee Foundation
- Agouron Institute
- Wellcome Trust
- Cancer Research UK
- European Commission
- Ministerstvo Školství, Mládeže a Tělovýchovy
- National Institutes of Health
- Horizon 2020 Framework Programme
- Horizon 2020
- National Institute of Diabetes and Digestive and Kidney Diseases
- H2020 Marie Skłodowska-Curie Actions