Abstract
SummaryEukaryotic 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.
Highlights
The RNA-guided targeting of nucleic acids is an ancient and conserved mechanism of cellular immunity that has been evolutionarily adapted and diversified to regulate eukaryotic gene expression
When we looked at protein-coding genes corresponding to previously defined PIWI-interacting RNAs (piRNAs)-dependent 22G-RNA targets—a category inferred based on global loss of total 22GRNAs upon piwi mutation (Barucci et al, 2020)—we found that only 18% showed altered transcription in piwi mutants (Figure 1A)
Spermatogenesis in the C. elegans hermaphrodite germline occurs during the L4 stage, preceding oogenesis that starts in young adult germlines (Figure S1A)
Summary
The RNA-guided targeting of nucleic acids is an ancient and conserved mechanism of cellular immunity that has been evolutionarily adapted and diversified to regulate eukaryotic gene expression. Non-sequence-specific mechanisms of piRNA-mediated gene regulation have been described (Shen et al, 2018; Vourekas et al, 2016), showing that piRNAs do not necessarily rely on perfect sequence complementarity to function. These features leave piRNAs as a sort of ‘‘specificity paradox’’ in the sequence-based regulation of gene expression, making it difficult to study their direct targets and biological functions
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