PIWI proteins and PIWI-interacting RNAs in the soma

The discoveries of small non-coding RNAs, including PIWI-interacting RNAs (piRNAs), have significantly expanded the RNA world. piRNAs are generally 24–32 nucleotides in length and bind specifically to the PIWI subfamily of Argonaute proteins. Piwi was originally discovered in Drosophila1, in which it functions in germline stem-cell maintenance and self-renewal2. For clarity, we use PIWIs to refer collectively to PIWI proteins, whereas Piwi refers to the individual protein. Although piRNAs were discovered and formally defined in mammalian systems in 2006 as small non-coding RNAs that specifically interact with PIWIs3-6, cloning of piRNAs in Drosophila7-9 revealed that they include a previously discovered class of small non-coding RNAs called repeat-associated RNAs (rasiRNAs)10,11. Since 2006, the PIWI–piRNA field has rapidly advanced, with a focus on the germ line, in which PIWIs and piRNAs are enriched and PIWI mutations lead to a profound infertility phenotype12-14. Indeed, the name PIWI comes from the original mutant phenotype P-element-induced wimpy testis1. The best-known role of the PIWI–piRNA pathway in the germ line is in transposon silencing, because piRNAs map largely to transposable elements9, with PIWI depletion leading to a drastic increase in transposon messenger RNA expression15. Despite the germline focus, since their discovery, PIWIs’ somatic function has long been documented. Initial work on the Drosophila gene piwi, the first identified member that defines the Argonaute gene family, determined that its germline function depends on the somatic cells of the gonad2. Recently, significant insight into the somatic function of the PIWI–piRNA pathway has come from the ovarian somatic cells of Drosophila. In addition, groundbreaking work in lower eukaryotes has demonstrated a conserved function for PIWIs and their associated piRNAs in somatic tissues — particularly in stem cells. In this Review, we focus on the role of the PIWI–piRNA pathway in the soma of diverse organisms, from basal eukaryotes to humans. We begin by looking at PIWI expression and piRNA biogenesis in somatic tissues, and then illustrate how the PIWI–piRNA pathway exerts diverse functions, including epigenetic regulation, transposon silencing, genome rearrangement and developmental regulation. Through this Review we hope to illustrate a broader role for the PIWI–piRNA pathway in the soma.