RT Journal Article SR Electronic T1 piRNA-guided co-transcriptional silencing coopts nuclear export factors JF bioRxiv FD Cold Spring Harbor Laboratory SP 611343 DO 10.1101/611343 A1 Martin H. Fabry A1 Filippo Ciabrelli A1 Marzia Munafò A1 Evelyn L. Eastwood A1 Emma Kneuss A1 Ilaria Falciatori A1 Federica A. Falconio A1 Gregory J. Hannon A1 Benjamin Czech YR 2019 UL http://biorxiv.org/content/early/2019/04/16/611343.abstract AB 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 gonads. In Drosophila, piRNA-guided silencing is achieved, in part, via co-transcriptional repression of transposons by Piwi. This depends on Panoramix (Panx); however, precisely how an RNA binding event silences transcription remains to be determined. Here we show that Nuclear Export Factor 2 (Nxf2) and its cofactor, 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 or Nxt1 to RNA 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.