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piRNA-guided co-transcriptional silencing coopts nuclear export factors.

Martin H Fabry | Filippo Ciabrelli | Marzia Munafò | Evelyn L Eastwood | Emma Kneuss | Ilaria Falciatori | Federica A Falconio | Gregory J Hannon | Benjamin Czech
eLife | 2019

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 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 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.

Pubmed ID: 31219034

Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: R37 GM062534
  • Agency: European Molecular Biology Organization, International
    Id: Long-Term Fellowship ALTF 1015-2017
  • Agency: Boehringer Ingelheim Fonds, International
    Id: PhD fellowship
  • Agency: Wellcome, International
    Id: Investigator award 110161/Z/15/Z

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