Sequence-dependent but not sequence-specific piRNA adhesion traps mRNAs to the germ plasm

Abstract

The conserved Piwi family of proteins and piwi-interacting RNAs (piRNAs) play a central role in genomic stability, which is inextricably tied with germ cell formation, by forming ribonucleoproteins (piRNPs) that silence transposable elements (TEs)1. In Drosophila melanogaster and other animals, primordial germ cell (PGC) specification in the developing embryo is driven by maternal mRNAs and proteins that assemble into specialized mRNPs localized in the germ (pole) plasm at the posterior of the oocyte2,3. Maternal piRNPs, especially those loaded on Aubergine (Aub), a Piwi protein, are transmitted to the germ plasm to initiate transposon silencing in the offspring germline4–7. Transport of mRNAs to the oocyte by midoogenesis is an active, microtubule-dependent process8; mRNAs necessary for PGC formation are enriched in the germ plasm at late oogenesis via a diffusion and entrapment mechanism, whose molecular identity remains unknown8,9. Aub is a central component of germ granule RNPs, which house mRNAs in the germ plasm10–12 and interactions between Aub and Tudor are essential for the formation of germ granules13–16. Here we show that Aub-loaded piRNAs use partial base pairing characteristic of Argonaute RNPs to bind mRNAs randomly, acting as an adhesive trap that captures mRNAs in the germ plasm, in a Tudor-dependent manner. Strikingly, germ plasm mRNAs in Drosophilids are generally longer and more abundant than other mRNAs, suggesting that they provide more target sites for piRNAs to promote their preferential tethering in germ granules. Thus complexes containing Tudor, Aub piRNPs and mRNAs couple piRNA inheritance with germline specification. Our findings reveal an unexpected function for Piwi ribonucleoprotein complexes in mRNA trapping that may be generally relevant to the function of animal germ granules.

A piRNA-lncRNA regulatory network initiates responder and trailer piRNA formation during mosquito embryonic development

“…piRNA-mediated gene regulation has been shown to be crucial in the embryonic development of both fruit flies and mosquitoes (Halbach, 2020, Rouget, Papin et al, 2010, Vourekas, Alexiou et al, 2016. Early embryonic development of animals is driven by maternally provided mRNAs until maternal-to-zygotic transition (MZT), during which the zygotic genome is activated and maternal mRNAs are degraded (Tadros & Lipshitz, 2009).…”

Ubiquitination-Deficient Mutations in Human Piwi Cause Male Infertility by Impairing Histone-to-Protamine Exchange during Spermiogenesis

“…Piwi proteins are known to enlist germline-specific Piwi-interacting RNAs (piRNAs) to suppress transposable elements and protect the integrity of the genome in germ cells (Juliano et al, 2011; Siomi et al, 2011). We and others recently showed that the Piwi/piRNA machinery also functions in regulating protein coding genes in germ cells (Gou et al, 2014; Zhang et al, 2015; Barckmann et al, 2015; Watanabe et al, 2015; Vourekas et al, 2016). Extensive genetic studies in worms, flies, fish, and mice indicate that Piwi proteins are essential for gametogenesis in animals (Cox et al, 1998; Harris and Macdonald, 2001; Deng and Lin, 2002; Kuramochi-Miyagawa et al, 2004; Carmell et al, 2007; Houwing et al, 2008; Batista et al, 2008).…”

Two modes of targeting transposable elements by piRNA pathway in human testis

“…Later in development, most postnatal piRNAs are produced from specific genomic regions termed piRNA clusters and divided into two types, depending on the stage of their expression: prepachytene clusters arising from genic sequences, and pachytene clusters of intergenic origin (Li et al 2013a). The details of both biogenesis and function of these two types of postnatal piRNAs in the developing testis remain unclear; however, several reports have proposed various hypotheses relating pachytene piRNAs to TE silencing or the control of gene expression in either an indiscriminate or targeted manner (Gou et al 2014;Hirano et al 2014;Goh et al 2015;Zhang et al 2015;Vourekas et al 2016).…”