Fig. 4

Similarities and differences between siRNA and piRNA pathways. Small interfering RNA (siRNA)-mediated RNAi pathway and piRNA pathway are ancient immune mechanisms against genome invaders. In both pathways, a small RNA associates with an Argonaute protein and mediates the sequence specific silencing of a target. SiRNAs associate with a member of the AGO subfamily of Argonaute proteins. PiRNAs are defined by their association with a PIWI-clade Argonaute protein. SiRNAs are defined by their biogenesis from long double stranded RNA (dsRNA) that is processed into small RNA duplexes by the RNase III enzyme Dicer. By contrast, fly and mouse piRNAs are generated from long, single stranded precursors in a Dicer-independent manner. Long single stranded RNAs (ssRNA) are processed by the conserved mitochondria-anchored endonuclease Zucchini (PLD6) or by the slicing activity of piRNA-guided PIWI proteins. SiRNAs guide the sequence-dependent slicing of a target RNA by their AGO protein partner, which exposes the target to exonucleolytic decay. Similarly, mature piRNAs mediate the slicing of complementary targets by their PIWI protein partner and induce target RNA decay. In addition to this post-transcriptional target regulation (PTGS), nuclear PIWI-piRNA complexes induce transcriptional gene silencing (TGS) by establishing restrictive epigenetic marks