Updated publication reference for PubMed record(s): 31219034. The PIWI-interacting RNA (piRNA) pathway is a small RNA-based immune system that controls the expression of transposons and maintains genome integrity in animal germlines1,2. In Drosophila, piRNA-guided silencing is achieved, in part, via co-transcriptional repression of transposons by Piwi. This depends on Panoramix (Panx)3,4; however, precisely how an RNA binding event silences transcription remains to be determined. Here we show that Nuclear Export Factor 2 (Nxf2) and its co-factor, Nxt1, form a complex with Panx, and are required for co-transcriptional silencing of transposons in somatic and germline cells of the ovary. Tethering of Nxf2 to either RNA or DNA results in silencing of target loci and the concomitant accumulation of repressive chromatin marks. Nxf2 and Panx proteins are mutually required for proper localization and stability. We mapped the protein domains crucial for the Nxf2/Panx complex formation and show that the amino-terminal portion of Panx is sufficient to induce transcriptional silencing. Loss of Nxf2 or Panx results in nuclear accumulation of transposon transcripts, which is for some transposons Piwi-dependent.