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

Cell Rep. 2024 Oct 22;43(10):114777. doi: 10.1016/j.celrep.2024.114777. Epub 2024 Sep 19.

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.

Keywords: CP: Molecular biology; PIWI; evolution; fertility; germ cell; mobile genetic element; piRNA; readthrough transcription; spermatogenesis; stress; transposon.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • DNA Transposable Elements / genetics
  • Dogs
  • Humans
  • Mammals* / genetics
  • Mice
  • Piwi-Interacting RNA
  • RNA, Small Interfering* / genetics
  • RNA, Small Interfering* / metabolism
  • Species Specificity

Substances

  • RNA, Small Interfering
  • DNA Transposable Elements
  • Piwi-Interacting RNA