ArticleNature structural & molecular biology2024
Mammalian PIWI-piRNA-target complexes reveal features for broad and efficient target silencing.
Article in Nature structural & molecular biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- Positive Selection Targeted Primate Genes that Encode Transposable Element Repressors.Genome biology and evolution · 2026Article
- PAIRNet: Predicting PIWI cleavage specificity via position-aware RNA interaction modeling.PLoS computational biology · 2026Article
- MUTACLASH: identifying functional small RNA target sites using crosslinking-induced mutations.RNA (New York, N.Y.) · 2026Article
- Peptide‑based therapeutics targeting the SLC39A14‑PIWIL2 fusion in hepatocellular carcinoma.Genomics & informatics · 2025Article
- Sex-stratified piRNA expression analysis reveals shared functional impacts of perinatal lead (Pb) exposure in murine hearts.Epigenetics · 2025Article
- Non-Coding RNAs and Their Role in Maintaining Epidermal Homeostasis.Current issues in molecular biology · 2025Review
- PIWI proteins tether the piRNA biogenesis machinery to mitochondria during mammalian spermatogenesis.The EMBO journal · 2025Article
- Transcriptional and post-transcriptional regulation of transposable elements and their roles in development and disease.Nature reviews. Molecular cell biology · 2025Review
- Integrating Inflammatory and Epigenetic Signatures in IBD-Associated Colorectal Carcinogenesis: Models, Mechanisms, and Clinical Implications.International journal of molecular sciences · 2025Review
- The Role of Ovarian Granulosa Cells Related-ncRNAs in Ovarian Dysfunctions: Mechanism Research and Clinical Exploration.Reproductive sciences (Thousand Oaks, Calif.) · 2025Review
- Mechanistic insights into RNA cleavage by human Argonaute2-siRNA complex.Cell research · 2025Article
- Current updates regarding biogenesis, functions and dysregulation of microRNAs in cancer: Innovative approaches for detection using CRISPR/Cas13‑based platforms (Review).International journal of molecular medicine · 2025Review
- Article
- A guide to the biogenesis and functions of endogenous small non-coding RNAs in animals.Nature reviews. Molecular cell biology · 2025Review
- Article
- Mammalian piRNA target prediction using a hierarchical attention model.BMC bioinformatics · 2025Article
- Cracking the code: how piRNA pathway shapes spermatogenesis and combats male infertility.Frontiers in cell and developmental biology · 2025Review
- Recent advances of PIWI-interacting RNA in cardiovascular diseases.Clinical and translational medicine · 2024Review
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The PIWI-interacting RNA (piRNA) pathway is an adaptive defense system wherein piRNAs guide PIWI family Argonaute proteins to recognize and silence ever-evolving selfish genetic elements and ensure genome integrity. Driven by this intensive host-pathogen arms race, the piRNA pathway and its targeted transposons have coevolved rapidly in a species-specific manner, but how the piRNA pathway adapts specifically to target silencing in mammals remains elusive. Here, we show that mouse MILI and human HILI piRNA-induced silencing complexes (piRISCs) bind and cleave targets more efficiently than their invertebrate counterparts from the sponge Ephydatia fluviatilis. The inherent functional differences comport with structural features identified by cryo-EM studies of piRISCs. In the absence of target, MILI and HILI piRISCs adopt a wider nucleic-acid-binding channel and display an extended prearranged piRNA seed as compared with EfPiwi piRISC, consistent with their ability to capture targets more efficiently than EfPiwi piRISC. In the presence of target, the seed gate-which enforces seed-target fidelity in microRNA RISC-adopts a relaxed state in mammalian piRISC, revealing how MILI and HILI tolerate seed-target mismatches to broaden the target spectrum. A vertebrate-specific lysine distorts the piRNA seed, shifting the trajectory of the piRNA-target duplex out of the central cleft and toward the PAZ lobe. Functional analyses reveal that this lysine promotes target binding and cleavage. Our study therefore provides a molecular basis for the piRNA targeting mechanism in mice and humans, and suggests that mammalian piRNA machinery can achieve broad target silencing using a limited supply of piRNA species.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.