Nuclear RNA export factor variant initiates piRNA-guided co-transcriptional silencing

Abstract

The PIWI-interacting RNA (piRNA) pathway preserves genomic integrity by repressing transposable elements (TEs) in animal germ cells. Among PIWI-clade proteins in Drosophila, Piwi transcriptionally silences its targets through interactions with cofactors, including Panoramix (Panx) and forms heterochromatin characterized by H3K9me3 and H1. Here, we identified Nxf2, a nuclear RNA export factor (NXF) variant, as a protein that forms complexes with Piwi, Panx, and p15. Panx-Nxf2-p15 complex formation is necessary in the silencing by stabilizing protein levels of Nxf2 and Panx. Notably, ectopic targeting of Nxf2 initiates co-transcriptional repression of the target reporter in a manner independent of H3K9me3 marks or H1. However, continuous silencing requires HP1a and H1. In addition, Nxf2 directly interacts with target TE transcripts in a Piwi-dependent manner. These findings suggest a model in which the Nxf2-Panx-p15 complex enforces the association of Piwi with target transcripts to trigger co-transcriptional repression, prior to heterochromatin formation in the nuclear piRNA pathway.\n\nHighlightsO_LINxf2 plays an essential role in the Piwi-piRNA pathway\nC_LIO_LIFormation of Piwi-Panx-Nxf2-p15 (PPNP) complexes stabilizes both Panx and Nxf2\nC_LIO_LIThe PPNP complex triggers transcriptional silencing before heterochromatin formation\nC_LIO_LINxf2 directly binds to target transcripts in a Piwi-dependent manner\nC_LI