Fig. 1

Two modes of piRNA production. In somatic cell, piRNA is mainly produced by Phasing processing pathways (Left part). First, piRNA precursor transcript is cleaved by PIWI/initiator piRNA to generate pre-pre piRNA, pre-pre piRNA binds to a new PIWI protein and is then cleaved into two parts by endonucerase (Zucchini in Drosophila or PLD6 in mice). The binding part of PIWI protein is the known intermediate piRNA (pre-piRNA), which generates mature response piRNA under the action of exonucerase (Trimmer/PNLDC1) and methyltransferase (Hen1). The remainder of the pre-pre piRNA is repeatedly bound by the PIWI protein at its 5' end and repeatedly cleaved by the Zucchini/PLD6 to produce a string of Trailing piRNA. In germ cell, piRNA is produced by the mutual cleavage of complementary transcripts from transposon and piRNA clusters mediated by Ago3 and Aub, called the “Ping-pang” cycle (Right part), resulting in pairs of piRNAs (“initiator” and “responder” piRNA) with a 10 base overlap at the 5’- end