A Small RNA-Based Immune System Defends Germ Cells against Mobile Genetic Elements

Figure 1

Mechanisms of “nonself” discrimination and adaptation in piRNA-guided defense against transposons in Drosophila. PiRNA clusters are genomic intervals that accumulate defunct fragments of transposable elements (TE) as a record of prior mobile activity. (1) Cluster regions are unidirectionally or bidirectionally transcribed and give rise to long presumably single stranded transcripts. PiRNA cluster transcripts are specifically processed into primary piRNAs by the consecutive action of at least two nucleases. The endonuclease Zucchini (Zuc) generates the 5′ terminus of a primary piRNA that is loaded into Piwi or Aubergine (Aub) and then trimmed by a 3′-5′ exonuclease. Piwi-piRNA complexes enter the nucleus and recruit chromatin modifying enzymes to silence transposon loci. In contrast, Aub-piRNA complexes initiate an adaptive response against transposon transcripts in cytoplasmic germ granules. (2) Aub and Ago3 engage in a feed-forward adaptation mechanism—the “ping-pong” cycle—that degrades transposon transcripts and concomitantly produces secondary piRNAs to selectively enhance the response against active elements. Through a feedback mechanism secondary piRNAs can initiate further Zuc-dependent piRNAs that are loaded into Piwi and Aub (Centromere (C), Telomere (T)).