Fig. 2. Compartmentalization of piRNA production and function. (A) Localization of Piwi-class Argonautes in the Drosophila ovary. Argonautes (red), DNA (blue). Argonaute 3 (Ago3, top) and Aubergine (Aub, middle) localize to the cytoplasm and nuage, which is a perinuclear structure rich in RNA-processing enzymes. Piwi (bottom) localizes predominantly to germline nuclei. (B) Model for compartmentalized production and function of piRNAs. (1) Sense (blue) and antisense (red) strands of piRNA `master control' regions are transcribed and (2) exported from the nucleus. (3) In the nuage, Aub-piRNA complexes cleave sense transcripts, leading to the production of sense-strand piRNAs that (4) associate with Ago3. (5) Ago3-piRNA complexes cleave antisense transcripts, producing piRNAs that (6) associate with Aub and Piwi. (7) Aub complexes remain in the nuage and cleave sense-strand complexes. (8) Piwi-piRNA complexes are imported into the nucleus, where they silence homologous genes in euchromatin and heterochromatin.