The nuclear exosome is required for Piwi-piRNA mediated co-transcriptional gene silencing [smallRNA-seq]

Co-transcriptional gene silencing mediated by small RNA pathways is primarily studied in the context of heterochromatin formation. These pathways are known to target nascent RNAs, yet their intersection with cellular processes determining the fate of the nascent transcripts remain unclear. We report that the nuclear exosome, the central cellular 3' to 5' exo-ribonuclease complex, is required for transposon repression through the Piwi-piRNA pathway in Drosophila. Using somatic ovarian cells, where piRNA biogenesis and piRNA-guided silencing are separated, we demonstrate that the three adaptor complexes of the nuclear exosome –PAXT, NEXT, and TRAMP– are redundantly required for degrading piRNA target transcripts. Furthermore, we identify two paralogous proteins, Creator-1 and Creator-2, as piRNA pathway factors that physically connect the exosome to the Piwi-silencing complex through a novel poly-proline binding domain. Our findings uncover an evolutionarily conserved principle whereby the nuclear RNA exosome is integral to diverse co-transcriptional silencing processes controlled by small RNAs. Overall design: Small RNA Sequencing (small-RNA-seq) analyis of small RNA expression changes in cultured ovarian somatic cells (OSCs) after siRNA mediated depletion of CG31510, CG7065, CG31510&CG7065, Dis3, RrP40, Rrp41, dZfc3h1&dZcchc8, or Mtr4, compring to control knockdown.