piRNAs initiate transcriptional silencing of spermatogenic genes during C. elegans germline development

Dev Cell. 2022 Jan 24;57(2):180-196.e7. doi: 10.1016/j.devcel.2021.11.025. Epub 2021 Dec 17.


Eukaryotic genomes harbor invading transposable elements that are silenced by PIWI-interacting RNAs (piRNAs) to maintain genome integrity in animal germ cells. However, whether piRNAs also regulate endogenous gene expression programs remains unclear. Here, we show that C. elegans piRNAs trigger the transcriptional silencing of hundreds of spermatogenic genes during spermatogenesis, promoting sperm differentiation and function. This silencing signal requires piRNA-dependent small RNA biogenesis and loading into downstream nuclear effectors, which correlates with the dynamic reorganization of two distinct perinuclear biomolecular condensates present in germ cells. In addition, the silencing capacity of piRNAs is temporally counteracted by the Argonaute CSR-1, which targets and licenses spermatogenic gene transcription. The spatial and temporal overlap between these opposing small RNA pathways contributes to setting up the timing of the spermatogenic differentiation program. Thus, our work identifies a prominent role for piRNAs as direct regulators of endogenous transcriptional programs during germline development and gamete differentiation.

Keywords: C. elegans; RNAi; epigenetics; fertility; germ granules; germline development; piRNAs; small RNAs; spermatogenesis; transcriptional silencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Argonaute Proteins / genetics
  • Argonaute Proteins / metabolism
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Cell Differentiation / genetics
  • DNA Transposable Elements / genetics
  • Gene Expression Regulation, Developmental / genetics*
  • Gene Silencing / physiology
  • Germ Cells / metabolism
  • Male
  • Phosphoenolpyruvate Sugar Phosphotransferase System / genetics
  • RNA Interference / physiology
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics*
  • RNA, Small Interfering / metabolism
  • Spermatogenesis / genetics*
  • Spermatogenesis / physiology
  • Transcription, Genetic / genetics


  • Argonaute Proteins
  • CSR-1 protein, C elegans
  • Caenorhabditis elegans Proteins
  • DNA Transposable Elements
  • HRDE-1 protein, C elegans
  • RNA, Messenger
  • RNA, Small Interfering
  • Phosphoenolpyruvate Sugar Phosphotransferase System
  • phosphoenolpyruvate-sorbose phosphotransferase