Fig. 3

piRNA biogenesis in mice. The A-MYB transcription factor initiates the transcription of precursor piRNAs from piRNA clusters. The long single-stranded transcript is cut by MitoPLD/Zucchini into piRNA intermediates, with the help of Shutdown and Hsp83 co-chaperones. The piRNA intermediates are incorporated into MIWI protein. The 3′ end is trimmed by exonuclease TDRKH and the 2′-O-methylate is added by methyltransferase Hen1. The ping-pong cycle then generates secondary piRNAs and amplifies both primary and secondary piRNAs. MIWI2 is localized to the nucleus upon piRNA loading. MILI combines with piRNA to trigger secondary piRNA biogenesis. MILI cuts the complimentary mRNA, which then combines with MIWI2. MIWI2 undergoes a similar process that targets the piRNA precursor and cleaves piRNA. The MIWI2-piRNA complex can translocate into the nucleus to recruit modification enzymes and causes DNA methylation or histone modification to silence gene expression