RNA-silencing induces target gene relocalization toward a specialized nuage domain

Argonaute small RNA pathways maintain genome integrity and fertility by enforcing the transgenerational silencing of transposons as well as many developmentally regulated germline genes. To propagate silencing, Argonaute pathways coordinate heterochromatin silencing with cycles of small RNA amplification. In animal germlines, mRNA surveillance is thought to occur within cytoplasmic perinuclear domains called nuage. In C. elegans 20-50 nuage droplets called P granules surround each pachytene germline nucleus. P granules are known to host many of the Argonaute small RNA systems that carry out transcriptome surveillance, but what if any specific roles P granules might play in Argonaute silencing have remained mysterious. Here we show that RNAi triggers the expansion of a unique P granule, which accumulates large amounts of the target RNA. As transcriptional silencing ensues, both alleles of the target gene relocate near the inner nuclear membrane (INM) directly adjacent this enlarged P granule. Similarly, during piRNA-mediated silencing, both alleles of a target gene reside adjacent to a P granule containing target RNA sequences. In an Argonaute mutant defective in piRNA silencing, the target RNA is released from nuage, and the target alleles dissociate from each other and from the INM. Our findings suggest that transcriptome-surveillance tasks are sub-divided between nuage domains that become specialized to coordinate small RNA silencing signals to their heterochromatin targets.