Fig. 4. Biogenesis of piRNAs and rasiRNAs. (A) Biogenesis of piRNAs. In mammals, piRNAs are likely to be processed from single-stranded (ss)RNA precursors, and are further processed by as yet undefined endonucleases (green) before being methylated (me) by methyltransferases. They associate with members of the Piwi subfamily to participate in transposon control and/or other germline-specific functions. (B) Biogenesis of D. melanogaster rasiRNAs/piRNAs. In D. melanogaster, rasiRNAs/piRNAs are also likely to be derived from ssRNA precursors and are further processed by endonucleases (green), including specific members of the Piwi subfamily (as shown in C), before being methylated (me) by methyltransferases. They associate with the Piwi subfamily to participate in histone methylation. Su(var)205 (suppressor of variegation 205) is a heterochromatin-associated protein. (C) Ping-Pong model of D. melanogaster piRNA biogenesis. After the piRNA-directed cleavage of transposon mRNA (piRNA in red; transposon mRNA in black and blue) by the Piwi family member Aubergine (AUB), the resulting blue strand (sense to the transposon mRNA) associates with AGO3, to guide cleavage of the rasiRNA cluster transcript (black and red) that produces additional piRNAs.