ArticleCell2017
Ubiquitination-Deficient Mutations in Human Piwi Cause Male Infertility by Impairing Histone-to-Protamine Exchange during Spermiogenesis.
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Article in Cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers, 2 of them syntheses that pooled it.
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137citing papers in PubMed, 2 pooled it
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Who cites it
137 citing papers in PubMed, 2 syntheses or guidelines pooled it, 260 citations in OpenAlex.
- A systematic review of the validated monogenic causes of human male infertility: 2020 update and a discussion of emerging gene-disease relationships.Human reproduction update · 2021Pooled it
- PIWI family proteins as prognostic markers in cancer: a systematic review and meta-analysis.Cellular and molecular life sciences : CMLS · 2020Pooled it
- The Role of RNA Interactions with PIWI in Regulating Gametogenesis, Fertilization, and Early Development Across Species.Reproductive sciences (Thousand Oaks, Calif.) · 2026Review
- PIWIL4 regulates gene expression and piRNA levels in RSV-infected airway epithelial cells.iScience · 2026Article
- PSMA8-Containing 20S Proteasome Regulates Spermiogenesis and Male Fertility.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- PANDORA-seq reveals human sperm sncRNA signature endowed with sperm quality assessment.Genes & diseases · 2026Article
- PIWI-Interacting RNAs in brain health and disease: biogenesis, mechanisms, and therapeutic horizons.Psychopharmacology · 2026Review
- ASB9 promotes ubiquitin-mediated degradation of TNP2 to facilitate histone-to-protamine transition in humans and mice.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- A homozygous PIWIL1 frameshift variant triggers azoospermia and reveals a strong selective constraint on germline genome integrity.Journal of assisted reproduction and genetics · 2026Article
- Unravelling male infertility through epigenetics: present understanding and future challenges.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- piR-16404 drives ferroptotic liver injury via CASTOR1/mTORC1/GPX4 dysregulation in HepG2 cells and mice: a novel toxicity mechanism of N, N-dimethylformamide.Archives of toxicology · 2026Article
- Pathogenic Variants in PET Complex Encoding GenesHuman mutation · 2026Article
- IGF2BP3 recognizes mThe EMBO journal · 2026Article
- Environmental and Genetic Perturbations of the Sperm Epigenome.Advances in experimental medicine and biology · 2026Review
- Dynamic architecture of mammalian paternal chromatin: histone-to-protamine exchange and post-fertilization reprogramming.Epigenetics & chromatin · 2025Review
- PIWIL4 regulates gene expression and piRNA levels in RSV-infected airway epithelial cells.bioRxiv : the preprint server for biology · 2025Article
- Evaluation of circANKLE2 & circL3MBTL4 -RNAs Expression in Fertile and Infertile Men.Biochemical genetics · 2025Article
- PIWIs Regulate Spermatogonia Self-Renewal and Differentiation by Wnt/β-Catenin Signaling Pathway inBiology · 2025Article
- Palmitoyltransferase ZDHHC19 regulates histone-to-protamine exchange during spermiogenesis in mice.Science advances · 2025Article
- Centrosome‑, mitotic spindle‑ and cytokinetic bridge‑specific compartmentalization of AGO2 protein in human liver cells undergoing mitosis: Non‑canonical, RNAi‑dependent, control of local homeostasis.Molecular medicine reports · 2025Article
77 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 6 institutions in 2 countries.
Lan-Tao GouState Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093-0651, USA.
Jun-Yan KangState Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
Peng DaiState Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
Xin WangState Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
Feng LiState Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
Shuang ZhaoState Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
Man ZhangState Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
Min-Min HuaState Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; Key Lab of Reproduction Regulation of NPFPC-Shanghai Institute of Planned Parenthood Research, Fudan University Reproduction and Development Institution, Shanghai 200032, China.
Yi LuKey Lab of Reproduction Regulation of NPFPC-Shanghai Institute of Planned Parenthood Research, Fudan University Reproduction and Development Institution, Shanghai 200032, China.
Yong ZhuDepartment of Andrology and PFD, Center for Men's Health, Department of ART, Institute of Urology, Urologic Medical Center Shanghai General Hospital, Shanghai Key Lab of Reproductive Medicine Shanghai Jiao Tong University, Shanghai, 200080, China.
Zheng LiDepartment of Andrology and PFD, Center for Men's Health, Department of ART, Institute of Urology, Urologic Medical Center Shanghai General Hospital, Shanghai Key Lab of Reproductive Medicine Shanghai Jiao Tong University, Shanghai, 200080, China.
Hong ChenDepartment of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
Li-Gang WuState Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
Dangsheng LiShanghai Information Center for Life Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Xiang-Dong FuDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093-0651, USA.
Jinsong LiState Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; School of Life Science and Technology, Shanghai Tech University, Shanghai 201210, China.
Hui-Juan ShiKey Lab of Reproduction Regulation of NPFPC-Shanghai Institute of Planned Parenthood Research, Fudan University Reproduction and Development Institution, Shanghai 200032, China. Electronic address: shihuijuan@sippr.org.cn.
Mo-Fang LiuState Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; School of Life Science and Technology, Shanghai Tech University, Shanghai 201210, China; Collaborative Innovation Center of Genetics and Development, Fudan University, Shanghai 200438, China. Electronic address: mfliu@sibcb.ac.cn.
Center for Excellence in Molecular Cell Science · CNFudan University · CNShanghai Jiao Tong University · CNUniversity of California San Diego · USShanghai Institutes for Biological Sciences · CNShanghaiTech University · CN
Funding
Functional RNA elements in the human genomeR01HG004659 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Kevin Daniel Corbett, Eugene Wei-Ming Yeo · 2008 to 2026
$12.4MFUNCTION ®ULATION OF THE HUMAN SPLICING FACTOR SC35R01GM049369 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FU, XIANG-DONG · 1993 to 2018
$7.2MRegulation of RNA metabolism and cell growth control by SR protein kinasesR01GM052872 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DOWDY, STEVEN F · 1996 to 2019
$5.4MNHGRI NIH HHS R01 HG004659NIGMS NIH HHS R01 GM049369NIGMS NIH HHS R01 GM052872
Abstract
Genetic studies have elucidated critical roles of Piwi proteins in germline development in animals, but whether Piwi is an actual disease gene in human infertility remains unknown. We report germline mutations in human Piwi (Hiwi) in patients with azoospermia that prevent its ubiquitination and degradation. By modeling such mutations in Piwi (Miwi) knockin mice, we demonstrate that the genetic defects are directly responsible for male infertility. Mechanistically, we show that MIWI binds the histone ubiquitin ligase RNF8 in a Piwi-interacting RNA (piRNA)-independent manner, and MIWI stabilization sequesters RNF8 in the cytoplasm of late spermatids. The resulting aberrant sperm show histone retention, abnormal morphology, and severely compromised activity, which can be functionally rescued via blocking RNF8-MIWI interaction in spermatids with an RNF8-N peptide. Collectively, our findings identify Piwi as a factor in human infertility and reveal its role in regulating the histone-to-protamine exchange during spermiogenesis.
Indexed as
MutationAnimalsArgonaute ProteinsAzoospermiaChromatinDisease Models, AnimalDNA-Binding ProteinsDNA Mutational AnalysisFemaleGene Knock-In TechniquesHistonesHumansIntronsMaleMicePedigreeArgonaute ProteinsChromatinDNA-Binding ProteinsHistonesPIWIL1 protein, humanProtaminesRNF8 protein, humanUbiquitin-Protein Ligases
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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.