Figure 3.
Ping-pong model of transposon silencing by Piwi family proteins in germ granules. Mechanistic details for Drosophila Piwi proteins Aub and Ago3 localized in perinuclear nuage are shown, however, mammals have similar mechanism [71,73,114]. Transposon mRNA exported from the nucleus is recognized by antisense piRNA bound to Aub and then cleaved between nucleotides complementary to nucleotides 10 and 11 of the antisense piRNA. After additional processing of the cleaved RNA, it becomes a sense piRNA which, in association with Ago3, base-pairs with piRNA precursor and, similar to Aub/antisense piRNA complex, cleaves that precursor to generate another antisense piRNA. In mammals, during the ping-pong cycle, antisense and sense piRNAs are bound to Miwi2 and Mili respectively [114]. In addition to transposon mRNA degradation in cytoplasmic germ granules, some Piwi proteins have been implicated in epigenetic silencing of transposon transcription in the nucleus by promoting heterochromatin formation or DNA methylation [73,114].