Biogenesis of piRNAs: piRNAs are generated from primary and secondary pathways. While most exhaustively explored in Drosophila, the general architecture of these pathways is largely conserved across animals. In the primary pathway, antisense primary piRNAs are cleaved by an endonuclease, most likely Zucchini. Cleaved precursors are incorporated in Aubergine (AUB) or Piwi, with a strong preference for uridine residues at the 5′ end. Subsequently, an exonuclease activity trims the 3′ end to a final length likely to be dictated by protection by the Piwi protein. The 3′ end is then methylated by the Hen enzyme. Aub-bound piRNAs can be amplified in the secondary pathway (ping-pong cycle), which involves the cleavage of a complementary sense transcript by Aub, its trimming, modification, and incorporation in a complex with AGO3. The final outcome is the inhibition of expression of piRNA targets by methylation at the DNA level and by a variety of post-transcriptional mechanisms (not shown in the figure, see text for details).