RNA Decay via the Nuclear Exosome is Essential for Piwi-Mediated Transposon Silencing [RNA-seq]

ABSTRACT: Small RNA pathways in the nucleus safeguard genome integrity by directing transcriptional silencing and heterochromatin formation at transposon loci. Yet, how these pathways achieve effective repression despite requiring transcription for Argonaute targeting has remained unclear. Here, we show that in Drosophila, the Piwi–piRNA pathway enforces transposon silencing through RNA degradation by the nuclear RNA exosome. Using comprehensive proximity proteomics at piRNA target sites combined with genetic analyses, we identify two previously uncharacterized paralogs, TEsup-1 and TEsup-2, which connect Piwi to nuclear exosome adaptor complexes via a distinct binding module for proline-rich peptides. Disruption of this Piwi–TEsup–exosome axis leads to accumulation and nuclear export of transposon RNAs. Strikingly, transposons that evade heterochromatin-based repression, exemplified by the P-element, are repressed primarily through this RNA-decay pathway. These findings reveal a molecular mechanism by which the nuclear piRNA-pathway couples target recognition to RNA degradation, providing a framework that reconciles small RNA-guided heterochromatin formation with ongoing transcription at target loci.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE313708 | GEO | 2025/12/19

REPOSITORIES: GEO