Figure 1

piRNA biogenesis. Two pathways, primary piRNA biogenesis and the Ping-Pong cycle, have been implicated in generation of piRNAs in Drosophila germ cells, whereas only primary piRNA biogenesis operates in follicular cells. Long RNAs transcribed from piRNA cluster regions are exported from the nucleus to nuage granules, where many protein components involved in the piRNA pathway localize and where piRNA biogenesis is believed to occur. During primary piRNA biogenesis long piRNA precursors are cleaved by an endonuclease, possibly Zucchini, located in the outer membrane of mitochondria, generating the 5′ end of the future piRNA. The cleaved transcript is loaded into Piwi proteins (Piwi and Aub) and then trimmed from the 3′ end by an unidentified trimmer nuclease to its final length. In the Ping-Pong cycle, Aub loaded with piRNAs recognizes and cleaves complementary RNAs such as transposon (TE) mRNAs or transcripts derived from the opposite strand of the same piRNA cluster. This cleavage produces the 5′ end of a new piRNA that is loaded into Ago3 and in turn can induce cleavage of complementary RNA. This generates a new piRNA that is identical in sequence to the piRNA that initiated the cycle.