Abstract
The Piwi-interacting RNA (piRNA) pathway is a small RNA-based immune system that silences mobile genetic elements in animal germlines. piRNA biogenesis requires a specialized machinery that converts long single-stranded precursors into small RNAs of ∼25-nucleotides in length. This process involves factors that operate in two different subcellular compartments: the nuage/Yb body and mitochondria. How these two sites communicate to achieve accurate substrate selection and efficient processing remains unclear. Here, we investigate a previously uncharacterized piRNA biogenesis factor, Daedalus (Daed), that is located on the outer mitochondrial membrane. Daed is essential for Zucchini-mediated piRNA production and the correct localization of the indispensable piRNA biogenesis factor Armitage (Armi). We found that Gasz and Daed interact with each other and likely provide a mitochondrial "anchoring platform" to ensure that Armi is held in place, proximal to Zucchini, during piRNA processing. Our data suggest that Armi initially identifies piRNA precursors in nuage/Yb bodies in a manner that depends on Piwi and then moves to mitochondria to present precursors to the mitochondrial biogenesis machinery. These results represent a significant step in understanding a critical aspect of transposon silencing; namely, how RNAs are chosen to instruct the piRNA machinery in the nature of its silencing targets.
Highlights
IntroductionThe Piwi-interacting RNA (piRNA) pathway acts in the germlines of animals as diverse as arthropods, amphibians, and mammals to control the expression of mobile genetic elements, protecting the genome from the potentially harmful consequences of uncontrolled transposon mobilization (Czech et al 2018; Ozata et al 2019). piRNAs function in complex with Argonaute proteins of the PIWI clade (in Drosophila, Piwi, Aubergine [Aub], and Argonaute-3 [Ago3]), guiding them to repress transposons at both transcriptional and posttranscriptional levels (Brennecke et al 2007; Gunawardane et al 2007; Sienski et al 2012; Le Thomas et al 2013; Rozhkov et al 2013; Czech et al 2018)
The Piwi-interacting RNA pathway acts in the germlines of animals as diverse as arthropods, amphibians, and mammals to control the expression of mobile genetic elements, protecting the genome from the potentially harmful consequences of uncontrolled transposon mobilization (Czech et al 2018; Ozata et al 2019). piRNAs function in complex with Argonaute proteins of the PIWI clade, guiding them to repress transposons at both transcriptional and posttranscriptional levels (Brennecke et al 2007; Gunawardane et al 2007; Sienski et al 2012; Le Thomas et al 2013; Rozhkov et al 2013; Czech et al 2018)
Depletion of CG10880 from the fly germline resulted in transposon derepression at levels comparable with those observed for knockdowns of zuc and gasz (Supplemental Fig. S1B) and in a strong delocalization of Piwi from nuclei, a hallmark of impaired piRNA biogenesis (Supplemental Fig. S1C)
Summary
The Piwi-interacting RNA (piRNA) pathway acts in the germlines of animals as diverse as arthropods, amphibians, and mammals to control the expression of mobile genetic elements, protecting the genome from the potentially harmful consequences of uncontrolled transposon mobilization (Czech et al 2018; Ozata et al 2019). piRNAs function in complex with Argonaute proteins of the PIWI clade (in Drosophila, Piwi, Aubergine [Aub], and Argonaute-3 [Ago3]), guiding them to repress transposons at both transcriptional and posttranscriptional levels (Brennecke et al 2007; Gunawardane et al 2007; Sienski et al 2012; Le Thomas et al 2013; Rozhkov et al 2013; Czech et al 2018). It is likely that a similar 5′-P precursor is generated without Aub or Ago in Yb bodies, but the underlying molecular mechanism for this process remains obscure Following this initial precursor specification, the production of mature Piwi-bound piRNAs occurs on the outer surface of mitochondria, where the conserved endonuclease Zucchini (Zuc) converts single-stranded. A number of cytosolic factors contribute to the process of piRNA biogenesis Among these is Armitage (Armi), an RNA helicase of the Upf family, which localizes to nuage and mitochondria in germ cells and predominantly to Yb bodies in follicle cells (Malone et al 2009; Olivieri et al 2010; Saito et al 2010). These data place Armi at a critical juncture in piRNA biogenesis, where its binding to precursor transcripts is both necessary and sufficient to specify downstream piRNA production by Zuc and its mitochondrial cofactors
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