One Loop to Rule Them All: The Ping-Pong Cycle and piRNA-Guided Silencing

Abstract

The PIWI-interacting RNA (piRNA) pathway is a conserved defense mechanism that protects the genetic information of animal germ cells from the deleterious effects of molecular parasites, such as transposons. Discovered nearly a decade ago, this small RNA silencing system comprises PIWI-clade Argonaute proteins and their associated RNA-binding partners, the piRNAs. In this review, we highlight recent work that has advanced our understanding of how piRNAs preserve genome integrity across generations. We discuss the mechanism of piRNA biogenesis, give an overview of common themes as well as differences in piRNA-mediated silencing between species, and end by highlighting known and emerging functions of piRNAs. Transcription and stabilization of piRNA precursors in Drosophila germ cells require the Rhino-Deadlock-Cutoff complex. Primary piRNA biogenesis takes place at Yb bodies and depends on the endonuclease Zucchini and several additional mitochondria-anchored factors. A tightly controlled, concerted interplay of Tudor proteins is necessary within the ping-pong cycle to ensure appropriate targeting of piRNA amplification. Secondary piRNA processing through the ping-pong cycle and primary piRNA biogenesis are interconnected. Transposon slicing results in the generation of phased piRNA populations that associate with Piwi and mediate transcriptional gene silencing. Transcriptional gene silencing via Piwi depends on Asterix and Panoramix, linking the piRNA pathway to the general silencing machinery.