Theoretical model of the primary biogenesis of piRNA and amplification via a ping-pong cycle. Zucchini endonuclease is thought to be responsible for the maturation of transcripts containing clusters of piRNA. Pre-piRNAs are recognised by a PIWI protein (Piwi A) with a preference for sequences with a uracil (U) in the first (5’) position. When associated with Piwi A, pre-piRNAs undergo maturation by a 3’-5’ exonuclease, as well as by HEN1 which adds a methyl group in 2’O of the 3’ end that makes them functional. The generated primary piRNAs can enter the ping-pong cycle. Through sequence complementarity, the primary piRNA directs the cleavage of the target retrotransposon (sense or antisense strand) thanks to the endonuclease activity brought by PIWI protein A. The newly generated 5’ end is recognised by another PIWI protein (Piwi B), but this protein can be the same as the first one. It is to be noted that the 3’ end of the secondary piRNA is matured and modified, just as the primary piRNA. The secondary piRNA can direct the cleavage activity of Piwi B on the transcript bearing piRNA clusters, thereby creating a new secondary piRNA which sequence is identical to that of the primary piRNA and so on. The piRNAs which 5’ end is formed by the action of Zucchini (or potentially another endonuclease) are called primary piRNAs and piRNAs which 5’ end is formed by PIWI proteins are called secondary piRNAs. piRNAs called A10 are secondary piRNAs while those called U1 may be primary or secondary.