PT  - JOURNAL ARTICLE
AU  - Julia Batki
AU  - Jakob Schnabl
AU  - Juncheng Wang
AU  - Dominik Handler
AU  - Veselin I. Andreev
AU  - Christian E. Stieger
AU  - Maria Novatchkova
AU  - Lisa Lampersberger
AU  - Kotryna Kauneckaite
AU  - Karl Mechtler
AU  - Dinshaw J. Patel
AU  - Julius Brennecke
TI  - The nascent RNA binding complex SFiNX licenses piRNA-guided heterochromatin formation
AID  - 10.1101/609693
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 609693
4099  - http://biorxiv.org/content/early/2019/04/17/609693.short
4100  - http://biorxiv.org/content/early/2019/04/17/609693.full
AB  - The PIWI-interacting RNA (piRNA) pathway protects animal 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 the cellular heterochromatin machinery, while Nxf2 binds the nascent target RNA and licenses co-transcriptional silencing. Our results reveal an unexpected, RNA-export independent role for Nxf2 in nuclear small RNA biology and suggest that NXF-variants, which have largely unknown function in animals, are functionally linked to the genome-transposon conflict.