ArticleMolecular cell2024
C19ORF84 connects piRNA and DNA methylation machineries to defend the mammalian germ line.
Article in Molecular cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Establishment of DNA methylation during primate germ cell development.Nature communications · 2026Article
- A mammalian-like piRNA pathway in Axolotl reveals the origins of piRNA-directed DNA methylation.The EMBO journal · 2026Article
- Article
- Spermatogenesis Beyond DNA: Integrated RNA Control of the Epitranscriptome and Three-Dimensional Genome Architecture.Current issues in molecular biology · 2026Review
- A PIWI protein-dependent DNA N6-adenine methylation pathway inbioRxiv : the preprint server for biology · 2026Article
- Developmental Phase-Specific Molecular Signatures and Signaling Pathways in Cryptorchidism-Induced Testicular Damage.Biomolecules · 2025Article
- Exosomal small non-coding RNA profiling and the role of PIWI-interacting RNA pathway genes in Lumpy skin disease virus-infected bovines.Animal bioscience · 2025Article
- Transposable elements in health and disease: Molecular basis and clinical implications.Chinese medical journal · 2025Review
- DNA methylation at retrotransposons protects the germline by preventing NRF1-mediated activation.EMBO reports · 2025Article
- Cancer cell SPOCD1 promotes colorectal cancer liver metastasis by activating the CXCL12/CXCR4 signaling pathway in cancer-associated fibroblasts.Journal of translational medicine · 2025Article
- Novel mutations in ZMYND15 are associated with male infertility with oligozoospermia/azoospermia.Journal of assisted reproduction and genetics · 2025Article
- Targeting Regulatory Noncoding RNAs in Human Cancer: The State of the Art in Clinical Trials.Pharmaceutics · 2025Review
- Insights into the role of hnRNPK in spermatogenesis via the piRNA pathway.Scientific reports · 2025Article
- Functional Investigation of a Novel PIWIL4 Mutation in Nonobstructive Azoospermia During the First Wave of Spermatogenesis.Biomolecules · 2025Article
- Theoretical perspectives and clinical applications of non-coding RNA in lung cancer metastasis: a systematic review.Discover oncology · 2025Review
- IFNγ regulates ferroptosis in KFs by inhibiting the expression of SPOCD1 through DNMT3A.Cell death discovery · 2025Article
- Cracking the code: how piRNA pathway shapes spermatogenesis and combats male infertility.Frontiers in cell and developmental biology · 2025Review
- Article
- Inherited defects of piRNA biogenesis cause transposon de-repression, impaired spermatogenesis, and human male infertility.Nature communications · 2024Article
Corrections and comments
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Authors and funding
21 authors at 10 institutions in 4 countries.
Funding
Abstract
In the male mouse germ line, PIWI-interacting RNAs (piRNAs), bound by the PIWI protein MIWI2 (PIWIL4), guide DNA methylation of young active transposons through SPOCD1. However, the underlying mechanisms of SPOCD1-mediated piRNA-directed transposon methylation and whether this pathway functions to protect the human germ line remain unknown. We identified loss-of-function variants in human SPOCD1 that cause defective transposon silencing and male infertility. Through the analysis of these pathogenic alleles, we discovered that the uncharacterized protein C19ORF84 interacts with SPOCD1. DNMT3C, the DNA methyltransferase responsible for transposon methylation, associates with SPOCD1 and C19ORF84 in fetal gonocytes. Furthermore, C19ORF84 is essential for piRNA-directed DNA methylation and male mouse fertility. Finally, C19ORF84 mediates the in vivo association of SPOCD1 with the de novo methylation machinery. In summary, we have discovered a conserved role for the human piRNA pathway in transposon silencing and C19ORF84, an uncharacterized protein essential for orchestrating piRNA-directed DNA methylation.
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Registered trials
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.