The nascent RNA binding complex SFiNX licenses piRNA-guided heterochromatin formation

Abstract

The PIWI-interacting RNA (piRNA) pathway protects genome integrity in part through establishing repressive heterochromatin at transposon loci. Silencing requires piRNA-guided targeting of nuclear PIWI proteins to nascent transposon transcripts, yet the subsequent molecular events are not understood. Here, we identify SFiNX (Silencing Factor interacting Nuclear eXport variant), an interdependent protein complex required for Piwi-mediated co-transcriptional silencing in Drosophila. SFiNX consists of Nxf2-Nxt1, a gonad-specific variant of the heterodimeric mRNA export receptor Nxf1-Nxt1, and the Piwi-associated protein Panoramix. SFiNX mutant flies are sterile and exhibit transposon de-repression because piRNA-loaded Piwi is unable to establish heterochromatin. Within SFiNX, Panoramix recruits heterochromatin effectors, Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

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

“…This is because we performed our analysis using cultured cell line OSCs, and took different timepoints after expression of Nxf2 (Fig ). The present study is the only one to consider time points as early as 48 h. The regulation observed at 96 h after transfection, representing later stages of TE silencing, was consistent with the observation by Batki et al (preprint: Batki et al , ). An important issue to be clarified is the mechanism by which the PPNP complex initiates the silencing of TEs.…”

“…Additionally, we all have shown that the UBA domain of Nxf2 associates with Panx, and the NTF2 domain associates with p15. Our group and Batki et al have shown that the first LRR domain with RNA binding activity is needed for the regulation of TEs (preprint: Batki et al , ), and we have further shown direct association of TE transcripts with Nxf2 (Fig ). Among these four groups, we were the only one which was able to observe the initial steps of the silencing.…”

“…Four groups including ours have obtained the similar findings regarding the essential role of Nxf2 in the Piwi–piRNA pathway rather than in nuclear RNA export (preprint: Batki et al , ; Fabry et al , , preprint: Zhao et al , ). We all have identified a new complex of Panx–Nxf2–P15, which associates with Piwi.…”

“…We all have identified a new complex of Panx–Nxf2–P15, which associates with Piwi. Although Batki et al and Fabry et al did not observe significant amount of Piwi peptides in their shotgun MS analysis of Panx immunoprecipitants, they showed the interaction between Panx‐Piwi in immunoprecipitation followed by Western blot analysis and their former studies (preprint: Batki et al , ; Fabry et al , ; Sienski et al , ; Yu et al , ). The inconsistency could be due to the immunoprecipitation conditions and/or antibodies used.…”

Assembly and Function of Gonad-Specific Non-Membranous Organelles in Drosophila piRNA Biogenesis

“…Aub and Ago3 are cytoplasmic and repress transposons post-transcriptionally [12,13]. Piwi is localized in the nucleus and represses transposons transcriptionally with co-factors, including Panoramix (Panx), Gtsf1, Nxf2, Nxt1/p15, Maelstrom (Mael), Eggless (Egg), histone linker H1, and HP1 [2,7,12,14,15,[30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47].…”