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In mice, a SPOCD1–TPR-dependent ‘nowhere-to-hide’ mechanism is required for complete non-stochastic piRNA-directed LINE1 DNA methylation by preventing transposons from escaping surveillance within heterochromatin.

24-nt phased siRNA (phasiRNA) regulate reproduction in grasses, yet are absent from Arabidopsis, and were thought to be monocot-specific. Here, Xia et al. show that 24-nt phasiRNAs are in fact broadly distributed among eudicots and are consistently enriched during meiosis, despite possibly arising from distinct biogenesis pathways.

The authors reveal that, in fruit fly ovaries, the protein Rhino is guided to specific regions of the genome by a combination of two histone modifications, enhancing understanding of how cells protect their DNA from harmful virus-like elements.

Piwi-interacting RNAs (piRNAs) are vital for genome integrity and fertility. Here the authors reveal that spatial clustering of piRNA genes in Caenorhabditis elegans promotes transcription through phase separation and deSUMOylation, uncovering a SUMOylation-regulated mechanism for piRNA production in heterochromatic genomes.

After target binding, PIWI proteins undergo a conformational change from ‘open’ to ‘locked’, facilitating base pairing and enhancing target cleavage efficiency, providing insights into how dynamic conformational changes from PIWI coordinate cofactors to safeguard gametogenesis.

Piwi-associated RNAs (piRNAs) are small RNAs with several functions in the germline, such as repressing transposable elements and helping to maintain germline stem cells. Now, a function for piRNAs has been discovered outside the germline, in the fruitfly embryo. Specifically, piRNAs are required for the decay of the messenger RNA encoding the posterior morphogen Nanos. When piRNA-induced regulation is impaired, this mRNA is stabilized and developmental defects ensue.

Phenotypic robustness in the face of genetic and environmental perturbations — known as canalization — relies on buffering mechanisms. Hsp90 chaperone machinery has been proposed to be an evolutionarily conserved buffering mechanism of phenotypic variance. Here, an additional, perhaps alternative, mechanism whereby Hsp90 influences phenotypic variation is proposed; Hsp90 mutations can generate new variation by transposon-mediated mutagenesis.

Zucchini has been identified as an endoribonuclease responsible for the maturation of small RNA molecules that protect the genome from the damaging effects of unrestrained expression of mobile elements.

MILI-mediated piRNA processing and amplification is not essential for all MIWI2 male germline reprogramming activity, indicating the existence of a MILI-independent piRNA biogenesis pathway.

piRNA processing factors and piRNA/PIWI complex are found in intermitochondrial cement (IMC) and chromatoid body (CB). Here, the authors show that piRNA loading orchestrates MIWI translocation from the IMC to CB, demonstrating its crucial role in spermatogenesis.

The molecular basis of metabolic reprogramming in stem cells are poorly understood. Here the authors show that piRNAs and PIWI proteins play a key role in activating glycolysis in germline stem cells through direct regulation of glycolytic mRNAs.

The role of PIWI proteins in mammalian reproduction remains poorly understood. Here, using golden hamsters, the authors establish expression profiles for all four PIWIs during gametogenesis and characterize their associated reproductive defects.

In male mouse germline development, the precise DNA methylation of young, active transposons requires a two-step process in which SPIN1 and SPOCD1 mark young LINE1 elements before the piRNA pathway triggers DNA methylation.

We find that massive genome expansion seems to be related to a reduction of PIWI-interacting RNAs and C2H2 zinc-finger and KRAB-domain protein genes that suppress transposable element expansion, and lungfish chromosomes still conservatively reflect the ur-tetrapod karyotype.

Bombyx Vasa assembles Vasa bodies, the site of transposon silencing by Siwi and Ago3-piRISC formation. Here, the authors show Vasa sequesters transposon mRNAs in Vasa bodies via phase separation requiring RNA binding and self-association of Vasa.

Phase separated, membrane-less germ granules preserve fertility and cellular function in animal germ cells. Here the authors show that loss of germ granules impacts piRNA pathway fidelity in the recognition of self and non-self nucleic acids.

This study provides structural and biochemical insight into how mammalian PIWI proteins use a limited supply of piRNAs to silence a vast array of ever-evolving transposons in the germline.

In Caenorhabditis tropicalis, selective expression of genetic alleles from one parent but not the other can arise from maternally inherited small transcripts acting via the PIWI-interacting RNA host defence pathway.

Siwi-piRISC protects the germline genome from DNA damage caused by selfish movement of transposons by suppressing their expression. Here, the authors show how molecularly Papi, which plays an important role in the production of Siwi-piRISC, cooperates with Par-1 kinase to ensure the accumulation of Siwi-piRISC in germ cells.

Piwi deficiency results in sterility and is associated with transposon expression and genomic instability. Here the authors show that sterility of C. elegans Piwi prg-1 mutant is not associated with transposon-induced DNA damage but is associated with and is phenocopied by dysfunction of germ granules.

A set of three papers reports that the piRNA pathway is essential for mammalian female fertility based on genetic perturbation experiments performed in golden hamsters.

PIWI protein contains arginine rich motifs that are post-translationally modified to symmetrically methylated arginine (sDMA) residues. Here the authors show that piRNA loading into Aub triggers sDMA modification which is recognized by Krimper to promote formation of Krimper-Aub-Ago3 complex for piRNA amplification in Drosophila.

Mature piRNAs are produced from long single-stranded precursor RNAs. Here the authors show that RNase κ generates 2′,3′-cyclic phosphate-containing piRNA precursors and promotes piRNA production.

Cryo-electron microscopy structures of a PIWI–piRNA complex provide insight into how piRNAs recognise target RNAs and reveal differences from the target mechanisms of microRNAs.

Piwi-interacting RNAs are small RNAs produced by processing of long precursor transcripts. Here the authors report that precursor cleavage typically occurs at positions corresponding to stop codons and that this pattern is conserved across mammals.

A set of three papers reports that the piRNA pathway is essential for mammalian female fertility based on genetic perturbation experiments performed in golden hamsters.

Here, the authors provide mechanistic evidence for the piRNA pathway connection to the heterochromatin machinery in Drosophila.

To control transposable elements, fruit flies rely on distinct genomic regions called piRNA clusters. Here, new piRNA clusters were identified across diverse Drosophila species, displaying a conserved and specialised role in the control of endogenous retroviruses in ovarian somatic cells.

A silkworm model recapitulates key steps of Zucchini-mediated cleavage of pre-pre-piRNA and provides insights into Zucchini-mediated and -independent pathways that generate pre-piRNAs, which converge to a common piRNA maturation step.

Zhao et al. identify an unexpected role of the nuclear export factor Nxf2 as a partner of Panoramix in mediating piRNA-guided silencing. Nxf2 counteracts Nxf1-centred nuclear RNA transport to prevent the export of transposon transcripts.

A conserved satellite repeat in the mosquito Aedes aegypti encodes PIWI-interacting RNAs that promote sequence-specific gene silencing in trans and have an essential role in embryonic development.

The C. elegans PIWI protein PRG-1 resides in the membraneless organelle P granule. Here, the authors identify the constitutive P granule protein DEPS-1 as an interactor of PRG-1 and show its function in piRNA-dependent silencing. DEPS-1 and PRG-1 form elongated condensates in vivo.

The PIWI protein MIWI2 counteracts transposon activity by transcriptional silencing in the mammalian germline. Here, the authors show that TEX15 interacts with MIWI2 and is required for piRNA-directed methylation of transposable elements in male germ cells.

Pachytene Piwi-interacting RNAs (piRNAs) expressed in mammalian germ lines are abundant, but their evolution and function are not fully understood. Here, the authors find that pachytene piRNA loci are hotspots of structural variation, which underlies rapid piRNA birth, divergence, and loss.

In Drosophila ovarian follicle cells, piRNAs generated from RNA precursors are processed in cytoplasmic Yb-bodies. The authors identify the exportin and the exon junction complexes as required to transfer precursors to cytoplasm. They also show that Yb-body formation requires piRNA precursor export.

A set of three papers reports that the piRNA pathway is essential for mammalian female fertility based on genetic perturbation experiments performed in golden hamsters.

Heterochromatin protein 1a (HP1a) is thought to function downstream of transposon repression in the Drosophila female germline. Here the authors show that HP1a also functions upstream of piRNA processing by repressing splicing of piRNA precursors, predominantly at telomeric and centromeric regions.

Barucci et al. show that the progressive loss of fertility in Caenorhabditis elegans lacking piRNAs is mediated by the epigenetic silencing of all of the replicative histone genes.

Gao et al. identify a piRNA, CHAPIR, that targets the m⁶A methylation of PARP10 and promotes the GSK3β-induced accumulation of nuclear NFATC4, thereby modulating cardiac hypertrophy and heart function upon pressure overload.

Identification of SFiNX, a complex of Nxf2–Nxt1, a variant of the mRNA export receptor Nxf1–Nxt1 and the Piwi-associated protein Panoramix, demonstrates an RNA export independent role for Nxf2 in piRNA-guided cotranscriptional transposon silencing.

The Piwi-interacting RNA (piRNA) pathway is known to suppress transposable elements in gonadal tissues. Here the authors provide evidence for a functional piRNA pathway in the somatic cells of theDrosophilafat body with roles in metabolism, immunological function and overall health.

piRNAs are regulatory RNAs that play a critical role in transposon silencing and gametogenesis. Here, the authors provide evidence that mammalian PNLDC1 is a regulator of piRNA biogenesis, transposon silencing and spermatogenesis, protecting the germline genome in mice.

PIWI-interacting RNAs (piRNAs) suppress transposon and gene expression during development. Here, the authors identify many piRNAs and piRNA-like small RNAs in 11 human cell lines, and show that one piRNA-like small RNA binds to phosphorylated ERM proteins to regulate cancer cell migration and invasion.

In Drosophila embryos, Piwi-interacting RNAs (piRNAs) loaded into the PIWI protein Aubergine target and destabilize maternal mRNAs. Here, the authors provide evidence that piRNAs and Aubergine cooperate with the Wispy poly(A) polymerase to stabilize these mRNAs in the germ plasm.

Pachytene piRNAs are abundant piRNAs in mammalian adult testes but their biogenesis pathway is not fully understood. Here, the authors identify TDRD5 as a piRNA biogenesis factor in mice, showing that it binds piRNA precursors and promotes pachytene piRNA production from specific transcript regions.

Piwi proteins bind a class of small germline RNAs, called piRNAs, whose biogenesis and functions are largely unknown. High-throughput sequencing after cross-linking and immunoprecipitation (HITS-CLIP) analysis in combination with RNA sequencing to analyze the genome-wide RNA target repertoire of mouse Piwi (Miwi) proteins in testis uncovers the in vivo piRNA biogenesis pathway and demonstrates that Miwi binds spermiogenic RNAs directly without using piRNAs as guides.

Haifan Lin and colleagues report the identification in Drosophila of a protein complex composed of Hsp90 Piwi, and the Hsp70/Hsp90 Organizing Protein Homolog (Hop) and demonstrate the function of this complex in buffering against morphological changes in a sensitized background.

Maternal mRNAs are tethered within the Drosophila germ plasm via base-pairing interactions between mRNAs and piRNPs containing the Aub Piwi protein; the preference for certain mRNAs to be tethered appears to be related to their longer length, which provides more potential piRNP-binding sites, and the results suggest a new role for piRNAs in germ-cell specification independent of their role in transposon silencing.

Piwi protein Miwi is shown to be a small RNA-guided RNase in mice; disrupting the catalytic activity of Miwi results in increased accumulation of LINE1 retrotransposon transcripts and male infertility.

The biogenesis of piRNAs in the silkworm Bombyx is simpler than in Drosophila, with the exonucleases Trim and Nbr having no major role, and the endonuclease Zuc acting at the 3′ rather than the 5′ end.