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Showing PIWIL4 — MIWI2 is a alias.

PIWIL4

Piwi-like protein 4 · UniProt Q7Z3Z4

Length
852 aa
Mass
96.6 kDa
Annotated
2026-06-10
40 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PIWIL4 (MIWI2/HIWI2) is a Piwi-clade piRNA-binding protein whose central role is the silencing of transposable elements through piRNA-guided establishment of repressive chromatin and de novo DNA methylation (PMID:17395546, PMID:18381894). In fetal male germ cells it is required for de novo DNA methylation of LINE-1 and IAP retrotransposon regulatory regions, and its loss derepresses transposons, causes meiotic arrest with elevated DNA double-strand breaks, and triggers progressive germ-cell loss (PMID:18381894, PMID:24464225). piRNA guides confer target specificity: MIWI2 binds nascent transcripts of piRNA-dependent regions, and deletion of the source retrotransposon sequence abolishes methylation of that locus (PMID:30108053). MIWI2 acts as a direct effector of de novo methylation — artificial targeting via a zinc-finger fusion is sufficient to methylate and silence LINE-1 and to partially rescue spermatogenesis (PMID:27626653) — recruiting downstream nuclear executors including TEX15 and MORC3 to direct methylation (PMID:32719317, PMID:34650118). In parallel it binds the H3K4 demethylases KDM1A and KDM5B to remove H3K4me2 marks at these loci, a step that precedes and permits DNA methylation (PMID:30304676). Its function is supported by piRNA-biogenesis and trafficking partners including TDRD9 and the EXD1–TDRD12 axis (PMID:20059948, PMID:30257204). Beyond the germline, PIWIL4 has somatic functions: it enforces HIV-1 latency by recruiting HP1, SETDB1, and HDAC4 to the proviral 5' LTR (PMID:32161174), and in AML cells it resolves R-loops on myeloid/leukemic-progenitor genes to suppress replication stress and ATR activation, an activity essential for leukemic stem cells but dispensable for normal hematopoietic stem cells (PMID:37146239). A piRNA-binding-impairing missense variant (p.R269W) derepresses LINE-1 during spermatogenesis, linking PIWIL4 piRNA function directly to its repressive role (PMID:40001600).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2007 High

    Established that a Piwi-clade protein is essential for germline transposon control, framing the core biological problem PIWIL4 solves.

    Evidence Miwi2 knockout mouse with histological and molecular phenotyping

    PMID:17395546

    Open questions at the time
    • Molecular mechanism of transposon silencing not defined
    • Direct effector activity not yet shown
  2. 2008 High

    Identified the molecular output of MIWI2 as de novo DNA methylation of retrotransposon promoters, connecting the protein to an epigenetic silencing pathway.

    Evidence MIWI2-null mouse with bisulfite sequencing of LINE-1/IAP and piRNA deep sequencing

    PMID:18381894

    Open questions at the time
    • Whether MIWI2 directly recruits methylation machinery vs. acts upstream unresolved
    • Target specificity determinant unknown
  3. 2009 High

    Placed MIWI2 in a piRNA-pathway protein network by identifying TDRD9 as a P-body partner regulated by MILI/TDRD1, clarifying the trafficking context of MIWI2 function.

    Evidence Reciprocal Co-IP, immunofluorescence, Tdrd9 knockout with methylation/piRNA readouts

    PMID:20059948

    Open questions at the time
    • Biochemical role of TDRD9 in silencing not defined
    • How P-body localization couples to nuclear methylation unclear
  4. 2014 High

    Defined the precise developmental window of MIWI2 action and the consequences of failure, showing transposon derepression causes meiotic arrest with DNA damage.

    Evidence Conditional Cre-lox Miwi2 knockout, γH2AX, retrotransposon RT-PCR, transcriptomics

    PMID:24464225

    Open questions at the time
    • Causal chain from transposon activation to DSBs not dissected
    • Effector proteins still unidentified
  5. 2015 High

    Distinguished MIWI2 from its paralog MILI in piRNA biogenesis and methylation target scope, showing non-redundant contributions to genome defense.

    Evidence Miwi2 and Mili knockout mice, piRNA deep sequencing, bisulfite sequencing across TE families

    PMID:26279574

    Open questions at the time
    • Basis for differential TE-family targeting unknown
  6. 2016 High

    Demonstrated MIWI2 is a direct, sufficient effector of de novo methylation by showing artificial targeting methylates and silences LINE-1 and rescues spermatogenesis.

    Evidence Transgenic ZF-MIWI2 fusion mouse, bisulfite sequencing, Co-IP of methylation machinery, MILI-null rescue

    PMID:27626653

    Open questions at the time
    • Identity of the recruited methylation effectors not fully resolved at this stage
  7. 2018 High

    Resolved how MIWI2 selects targets, showing piRNAs base-pair with nascent transcripts to direct chromatin/methylation changes at the source locus.

    Evidence MIWI2 RIP, in vivo CRISPR deletion of retrotransposon sequence, bisulfite sequencing

    PMID:30108053

    Open questions at the time
    • Stoichiometry and kinetics of transcript engagement not measured
  8. 2018 High

    Showed PIWIL4 also clears permissive H3K4me2 marks via KDM1A/KDM5B prior to methylation, establishing a chromatin-priming step in the silencing cascade.

    Evidence Co-IP of PIWIL4 with KDM1A/KDM5B, H3K4me2 ChIP-seq in Miwi2-null testes, bisulfite sequencing

    PMID:30304676

    Open questions at the time
    • Order of demethylase recruitment relative to nascent-transcript binding not fully resolved
  9. 2018 High

    Defined an upstream biogenesis input by showing EXD1/TDRD12 supply MIWI2 piRNAs, with loss derepressing LINE-1 and causing infertility.

    Evidence Exd1 knockout and compound mutant mice, precursor reporter assay, piRNA deep sequencing

    PMID:30257204

    Open questions at the time
    • Mechanism of phased piRNA generation feeding MIWI2 not fully reconstituted
  10. 2018 Medium

    Extended PIWIL4 function to somatic post-transcriptional regulation, showing piRNA-directed knockdown of FTH1 mRNA in breast cancer cells.

    Evidence piRNA transfection, HIWI2/HILI siRNA knockdown, FTH1 RT-PCR/western, viability assay

    PMID:30102404

    Open questions at the time
    • No biochemical reconstitution of cleavage
    • Dependence on both HIWI2 and HILI mechanistically unexplained
  11. 2020 High

    Identified TEX15 as an essential nuclear executor downstream of MIWI2 for methylation, separating effector function from piRNA biogenesis.

    Evidence Co-IP of MIWI2 and TEX15, Tex15 knockout, bisulfite and piRNA sequencing

    PMID:32719317

    Open questions at the time
    • Direct enzymatic role of TEX15 in methylation deposition not defined
  12. 2021 Medium

    Added MORC3 as a MIWI2 partner required for both methylation and piRNA precursor transcription, indicating feedback between effector and biogenesis.

    Evidence Co-IP of MORC3 with MIWI2, Morc3 knockout, bisulfite and piRNA sequencing

    PMID:34650118

    Open questions at the time
    • Single lab Co-IP
    • How MORC3 couples precursor transcription to methylation unresolved
  13. 2020 Medium

    Showed PIWIL4 enforces retroviral latency in somatic immune cells by recruiting heterochromatin machinery to the HIV-1 LTR, generalizing its silencing role beyond endogenous transposons.

    Evidence PIWIL4 knockdown, Co-IP with HP1/SETDB1/HDAC4, LTR ChIP, HIV-1 transcription assays in T cells

    PMID:32161174

    Open questions at the time
    • piRNA dependence of LTR targeting not established
    • Single lab
  14. 2023 High

    Revealed a distinct enzymatic role: PIWIL4 resolves R-loops on cancer/myeloid genes in AML to limit replication stress and ATR activation, defining a leukemia-specific dependency.

    Evidence PIWIL4 depletion in AML lines/patient samples, RIP-seq, R-loop detection, γH2AX, ATR assays, xenografts

    PMID:37146239

    Open questions at the time
    • Direct R-loop resolving biochemistry not reconstituted
    • piRNA guidance of this activity unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PIWIL4 switches between germline DNA-methylation effector, somatic mRNA regulator, and R-loop-resolving enzyme — and which partners/piRNAs dictate each mode — remains unresolved.
  • No unifying structural/biochemical model across contexts
  • Determinants selecting nuclear vs. cytoplasmic function unknown
  • Causal role of context-specific piRNAs largely correlative

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 4 GO:0060090 molecular adaptor activity 4 GO:0140098 catalytic activity, acting on RNA 3
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 3 GO:0005635 nuclear envelope 1
Pathway
R-HSA-4839726 Chromatin organization 4 R-HSA-1643685 Disease 2 R-HSA-8953854 Metabolism of RNA 2 R-HSA-73894 DNA Repair 1
Partners
GTSF1HSP90AA1KDM1AKDM5BMORC3SETDB1TDRD9TEX15

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 MIWI2 (PIWIL4) is essential for spermatogenesis; Miwi2-deficient mice display meiotic-progression defect in early prophase of meiosis I, progressive loss of germ cells, and inappropriate activation of transposable elements, establishing a conserved function for Piwi-clade proteins in transposon control in the germline. Miwi2 knockout mouse model with histological and molecular phenotypic analysis Developmental cell High 17395546
2008 MIWI2 is required for de novo DNA methylation of retrotransposon regulatory regions (LINE-1 and IAP) in fetal male germ cells; loss of MIWI2 impairs de novo methylation and reduces piRNA expression in fetal prospermatogonia. MIWI2-null mouse analysis with bisulfite sequencing of retrotransposon promoters and piRNA profiling by deep sequencing Genes & development High 18381894
2009 TDRD9 forms a complex with MIWI2 in processing bodies (P-bodies), and this TDRD9-MIWI2 localization is regulated by MILI and TDRD1 residing at intermitochondrial cement; TDRD9 is a functional partner of MIWI2 in piRNA-mediated LINE-1 silencing and DNA methylation in prospermatogonia. Co-immunoprecipitation, immunofluorescence/confocal microscopy, Tdrd9 knockout mouse with piRNA profiling and LINE-1 methylation analysis Developmental cell High 20059948
2007 Human PIWIL4, the only ubiquitously expressed PIWI-like family member, localizes to the nuclear periphery when expressed as a Flag-fusion protein and induces histone H3 lysine 9 methylation (H3K9me) at the p16Ink4a (CDKN2A) locus, resulting in downregulation of p16Ink4a gene expression. Transient transfection of Flag-PIWIL4, chromatin immunoprecipitation (ChIP) for H3K9 methylation, RT-PCR for p16Ink4a expression, immunofluorescence for localization Biochemical and biophysical research communications Medium 17544373
2014 Conditional inactivation of Miwi2 demonstrates that MIWI2 function is restricted to prospermatogonial development (primordial germ cell reprogramming window); persistent LINE1 and IAP retrotransposon activation from Miwi2 loss is compatible with mitotic spermatogonial proliferation but causes zygotene-to-pachytene meiotic arrest associated with enhanced DNA double-strand breaks, aberrant histone modifications, and altered mRNA transcriptome. Conditional (Cre-lox) Miwi2 knockout mouse, γH2AX staining, retrotransposon RT-PCR, FACS cell cycle analysis, transcriptome profiling Cell death and differentiation High 24464225
2015 MIWI2 and MILI have distinct roles in transposon repression: Miwi2 deficiency had minor impact on piRNA biogenesis overall but caused overexpression of specific LINE1 families that activated ping-pong piRNA cycling; MILI is responsible for DNA methylation of a larger subset of TE families than MIWI2, indicating independent roles in establishing DNA methylation patterns. Miwi2-knockout mouse, deep sequencing of piRNAs, bisulfite sequencing of TE loci, comparison with Mili-knockout Cell reports High 26279574
2016 ZF-MIWI2 fusion protein (MIWI2 fused to a zinc finger targeting LINE-1 type A promoter) induces de novo DNA methylation and suppression of LINE-1 type A, and partially rescues spermatogenesis in MILI-null mice; ZF-MIWI2 associates with proteins involved in DNA methylation machinery, establishing MIWI2 as a direct effector of de novo DNA methylation. Transgenic mouse expressing ZF-MIWI2 fusion protein, bisulfite sequencing, RT-PCR, Co-immunoprecipitation of DNA methylation proteins, spermatogenesis rescue assay in MILI-null background Cell reports High 27626653
2018 MIWI2 specifically interacts with RNAs transcribed from piRNA-dependent regions in prospermatogonia; deletion of a retrotransposon sequence from a piRNA-dependent region or piRNA cluster ablates DNA methylation of that region, indicating that piRNAs determine MIWI2 target specificity through base-pairing with nascent transcripts to affect chromatin state. RNA immunoprecipitation (RIP) of MIWI2, CRISPR deletion of retrotransposon sequence in mice, bisulfite sequencing The EMBO journal High 30108053
2018 PIWIL4/MIWI2 binds H3K4 demethylases KDM1A and KDM5B and is required for removal of H3K4me2 marks at piRNA-dependent DNA methylation regions; H3K4me2 is anti-correlated with de novo DNA methylation, and PIWIL4-mediated H3K4me2 demethylation precedes piRNA-dependent DNA methylation. Co-immunoprecipitation of PIWIL4 with KDM1A and KDM5B, ChIP-seq for H3K4me2 in wild-type and Miwi2-null fetal testes, bisulfite sequencing Cell reports High 30304676
2018 EXD1 enhances MIWI2 piRNA biogenesis through a functional interaction with TDRD12; in the Exd1 mutant, MILI-triggered phased piRNA biogenesis is greatly reduced, and in the sensitized Exd1−/−;Tdrd12+/− background, diminished MIWI2 piRNA levels de-repress LINE1 retrotransposons, leading to infertility. Exd1 knockout mouse, artificial piRNA precursor reporter assay, deep sequencing of piRNAs, retrotransposon RT-PCR, compound mutant analysis Cell reports High 30257204
2018 Human HIWI2 (PIWIL4) mediates piRNA (piR-FTH1)-directed post-transcriptional knockdown of ferritin heavy chain 1 (FTH1) mRNA in somatic (triple-negative breast cancer) cells; this piRNA-mediated repression requires both HIWI2 and HILI. piRNA transfection, HIWI2/HILI knockdown by siRNA, RT-PCR and western blot for FTH1, cell viability assay Nucleic acids research Medium 30102404
2014 Human HIWI2 (PIWIL4) is ubiquitously expressed in somatic cells; in cancer cells the protein is largely restricted to the cytoplasm and associates with translating ribosomes; immunoprecipitation of HIWI2 from MDA-MB-231 cells enriches for piRNAs predominantly derived from processed tRNAs and expressed genes, suggesting a somatic function linked to translation. Immunoprecipitation of HIWI2 followed by small RNA sequencing, polysome fractionation, immunofluorescence Nucleic acids research Medium 25038252
2020 TEX15 associates with MIWI2 in foetal gonocytes; TEX15 is predominantly nuclear and is not required for piRNA biogenesis but is essential for piRNA-directed de novo DNA methylation and transposon silencing, identifying TEX15 as an essential executor downstream of MIWI2 in directing DNA methylation. Co-immunoprecipitation of MIWI2 and TEX15, Tex15 knockout mouse, bisulfite sequencing, piRNA sequencing, immunofluorescence Nature communications High 32719317
2021 MORC3 is a novel associating partner of MIWI2 in embryonic testis; MORC3 is a nuclear effector required for piRNA-dependent de novo DNA methylation of retrotransposons and for transcription of piRNA precursors, thereby affecting piRNA production. Co-immunoprecipitation of MORC3 with MIWI2, Morc3 knockout mouse, bisulfite sequencing, piRNA sequencing, immunofluorescence Scientific reports Medium 34650118
2019 Under oxidative stress in retinal pigment epithelial (RPE) cells, PIWIL4 is first translocated to the nucleus and then sequestered into cytoplasmic stress granules, resulting in Alu RNA accumulation; sequestration of PIWIL4 correlates with mesenchymal transition of RPE cells. H2O2 treatment of RPE cells, immunofluorescence tracking of PIWIL4 localization, Alu RNA quantification, epithelial-mesenchymal transition marker analysis BMB reports Medium 30103846
2020 PIWIL4 maintains HIV-1 latency by recruiting heterochromatin protein 1α/β/γ, SETDB1, and HDAC4 to the HIV-1 5' LTR, imposing repressive epigenetic marks; PIWIL4 knockdown enhances HIV-1 transcription and reverses latency in Jurkat T cells and primary CD4+ T cells from cART-treated HIV-1-infected individuals. PIWIL4 knockdown by siRNA/shRNA, Co-immunoprecipitation of PIWIL4 with HP1α/β/γ, SETDB1, HDAC4, HIV-1 transcription assays (luciferase, p24 ELISA), ChIP at 5'LTR Journal of virology Medium 32161174
2016 HIWI2 knockdown in retinal pigment epithelial cells disrupts typical honeycomb cell morphology, alters expression of tight junction proteins CLDN1 and TJP1, and increases phosphorylation of Akt and GSK3α/β; pharmacological inhibition of PI3K with wortmannin rescues TJP1 and CLDN1 levels, indicating HIWI2 maintains epithelial tight junction integrity via the Akt-GSK3α/β signaling axis. siRNA knockdown of HIWI2, phospho-kinase proteome profiler array, confocal imaging of TJP1, western blot, wortmannin rescue experiment Molecular and cellular biochemistry Medium 28025795
2023 PIWIL4 functions as an R-loop resolving enzyme in AML cells: it binds mRNAs from coding regions and enhancers enriched for cancer/myeloid progenitor genes, prevents R-loop accumulation on AML/LSC-associated genes to maintain their expression, and suppresses DNA damage, replication stress, and ATR pathway activation; PIWIL4 is essential for leukemic stem cell function and AML growth but dispensable for healthy hematopoietic stem cells. PIWIL4 knockdown/depletion in AML cell lines and patient samples, RNA immunoprecipitation-seq, R-loop detection (DRIP-seq or S9.6 immunofluorescence), γH2AX assay, ATR pathway activation assays, colony/xenograft AML growth assay, pharmacological ATR inhibitor sensitization Blood High 37146239
2016 PIWIL4 promotes migration of MDA-MB-231 breast cancer cells and inhibits apoptosis; transcriptome and proteome analysis following PIWIL4 knockdown reveals dysregulation of TGF-β and FGF signaling pathways and MHC class II proteins as downstream effectors. siRNA knockdown of PIWIL4, transwell migration assay, apoptosis assay, RNA-seq transcriptome analysis, proteome profiling The Journal of biological chemistry Medium 26957540
2025 The piR-31115/PIWIL4 complex promotes migration of MDA-MB-231 TNBC cells by enhancing PIWIL4 binding to HSP90AA1, protecting HSP90AA1 from degradation; knockdown of HSP90AA1 attenuates the pro-migratory effect of piR-31115/PIWIL4. RNA immunoprecipitation (RIP) for piR-31115 binding to PIWIL4, Co-IP combined with mass spectrometry to identify PIWIL4-interacting proteins under piR-31115 modulation, transwell migration assay, western blot for HSP90AA1 Gene Medium 39842649
2025 A missense variant in PIWIL4 (c.805 C>T, p.R269W) alters piRNA-binding ability of PIWIL4 and leads to derepression of LINE-1 elements and aberrant gene expression during the first wave of spermatogenesis in homozygous knock-in mice, despite normal sperm counts and morphology. CRISPR knock-in mouse model, retrotransposon RT-PCR, RNA-seq transcriptome analysis, piRNA binding assay Biomolecules Medium 40001600
2024 piR-43452 recruits the GTSF1/PIWIL4 complex to the 3'UTR of LRP1 mRNA, enhancing target mRNA cleavage through GTSF1-dependent conformational activation of PIWIL4, leading to LRP1 suppression and inhibition of bladder cancer proliferation and chemoresistance. RNA immunoprecipitation, Co-immunoprecipitation of GTSF1 and PIWIL4, luciferase 3'UTR reporter assay, in vitro and in vivo proliferation/migration assays, knockdown experiments Translational oncology Medium 41344056
2024 piR-713551/PIWIL4 complex activates THBS2 transcription by recruiting histone demethylase KDM4A to reduce H3K9me3 modification at the THBS2 gene promoter in bronchial epithelial cells exposed to carbon black, contributing to epithelial-mesenchymal transition and pulmonary fibrosis. piR-713551 and PIWIL4 manipulation in BEAS-2B cells and CB-exposed mice, ChIP for H3K9me3 and KDM4A at THBS2 promoter, Co-IP of PIWIL4 with KDM4A, RT-PCR and western blot Journal of environmental sciences (China) Medium 40246476
2019 MIWI2 is transiently expressed during fibroblast-to-hepatocyte transdifferentiation; MIWI2 knockout improves induced hepatocyte formation while MIWI2 overexpression abolishes it; bioinformatics and experimental validation identified the Notch signaling pathway as an effector of MIWI2 during this process, indicating MIWI2 negatively regulates cell plasticity in somatic lineage reprogramming. MIWI2 knockout and overexpression during lineage reprogramming, piRNA profiling, bioinformatics piRNA interaction network analysis with experimental validation of Notch pathway Stem cells Low 30805989
2017 MIWI2 protein localizes to the cytoplasm of a discrete subset of multiciliated airway epithelial cells; mice lacking MIWI2 exhibit fewer multiciliated cells, more club cells, and enhanced inflammatory mediator expression and bacterial clearance during pneumococcal pneumonia, demonstrating a somatic role for MIWI2 in airway cell identity and pulmonary innate immunity. Miwi2-knockout mouse, immunofluorescence, cell-type-specific isolation and RNA-seq, bacterial challenge model The Journal of clinical investigation Medium 28920925

Source papers

Stage 0 corpus · 40 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 MIWI2 is essential for spermatogenesis and repression of transposons in the mouse male germline. Developmental cell 909 17395546
2008 DNA methylation of retrotransposon genes is regulated by Piwi family members MILI and MIWI2 in murine fetal testes. Genes & development 725 18381894
2009 The TDRD9-MIWI2 complex is essential for piRNA-mediated retrotransposon silencing in the mouse male germline. Developmental cell 275 20059948
2016 CRNDE Promotes Malignant Progression of Glioma by Attenuating miR-384/PIWIL4/STAT3 Axis. Molecular therapy : the journal of the American Society of Gene Therapy 173 27058823
2014 The human Piwi protein Hiwi2 associates with tRNA-derived piRNAs in somatic cells. Nucleic acids research 116 25038252
2015 MIWI2 and MILI Have Differential Effects on piRNA Biogenesis and DNA Methylation. Cell reports 83 26279574
2016 The Role of PIWIL4, an Argonaute Family Protein, in Breast Cancer. The Journal of biological chemistry 62 26957540
2007 The induction of H3K9 methylation by PIWIL4 at the p16Ink4a locus. Biochemical and biophysical research communications 61 17544373
2020 TEX15 is an essential executor of MIWI2-directed transposon DNA methylation and silencing. Nature communications 55 32719317
2018 MIWI2 targets RNAs transcribed from piRNA-dependent regions to drive DNA methylation in mouse prospermatogonia. The EMBO journal 44 30108053
2012 PIWIL4 regulates cervical cancer cell line growth and is involved in down-regulating the expression of p14ARF and p53. FEBS letters 44 22483988
2016 MIWI2 as an Effector of DNA Methylation and Gene Silencing in Embryonic Male Germ Cells. Cell reports 41 27626653
2018 A piRNA utilizes HILI and HIWI2 mediated pathway to down-regulate ferritin heavy chain 1 mRNA in human somatic cells. Nucleic acids research 37 30102404
2014 Conditional inactivation of Miwi2 reveals that MIWI2 is only essential for prospermatogonial development in mice. Cell death and differentiation 32 24464225
2011 Icariin induces apoptosis in mouse MLTC-10 Leydig tumor cells through activation of the mitochondrial pathway and down-regulation of the expression of piwil4. International journal of oncology 29 21687940
2018 Relationship between PIWIL4-Mediated H3K4me2 Demethylation and piRNA-Dependent DNA Methylation. Cell reports 21 30304676
2022 HIWI2 induces G2/M cell cycle arrest and apoptosis in human fibrosarcoma via the ROS/DNA damage/p53 axis. Life sciences 20 35074406
2018 Exonuclease Domain-Containing 1 Enhances MIWI2 piRNA Biogenesis via Its Interaction with TDRD12. Cell reports 20 30257204
2016 Possible role of HIWI2 in modulating tight junction proteins in retinal pigment epithelial cells through Akt signaling pathway. Molecular and cellular biochemistry 20 28025795
2019 Oxidative stress causes Alu RNA accumulation via PIWIL4 sequestration into stress granules. BMB reports 19 30103846
2023 A noncanonical enzymatic function of PIWIL4 maintains genomic integrity and leukemic growth in AML. Blood 18 37146239
2017 HIWI2 rs508485 Polymorphism Is Associated with Non-obstructive Azoospermia in Iranian Patients. Reports of biochemistry & molecular biology 18 28367472
2017 PIWI-like protein, HIWI2 is aberrantly expressed in retinoblastoma cells and affects cell-cycle potentially through OTX2. Cellular & molecular biology letters 17 28861107
2017 Expression of Piwi protein MIWI2 defines a distinct population of multiciliated cells. The Journal of clinical investigation 16 28920925
2020 PIWIL4 Maintains HIV-1 Latency by Enforcing Epigenetically Suppressive Modifications on the 5' Long Terminal Repeat. Journal of virology 15 32161174
2020 The Clinical Significance of PIWIL3 and PIWIL4 Expression in Pancreatic Cancer. Journal of clinical medicine 14 32357464
2018 PIWI-like protein, HIWI2: A novel player in proliferative diabetic retinopathy. Experimental eye research 14 30145353
2013 Deficiency of MIWI2 (Piwil4) induces mouse erythroleukemia cell differentiation, but has no effect on hematopoiesis in vivo. PloS one 12 24376547
2021 MORC3, a novel MIWI2 association partner, as an epigenetic regulator of piRNA dependent transposon silencing in male germ cells. Scientific reports 10 34650118
2022 PLIC11 drives lung cancer progression through regulating the YY1/PIWIL4 axis. Molecular carcinogenesis 7 36537719
2023 The role of PIWIL4 and piRNAs in the development of choroidal neovascularization. Genomics 5 36934857
2025 The piR-31115-PIWIL4 complex promotes the migration of the triple-negative breast cancer cell lineMDA-MB-231 by suppressing HSP90AA1 degradation. Gene 3 39842649
2024 Carbon black induced pulmonary fibrosis through piR-713551/PIWIL4 targeting THBS2 signal pathway. Journal of environmental sciences (China) 3 40246476
2019 Somatic MIWI2 Hinders Direct Lineage Reprogramming From Fibroblast to Hepatocyte. Stem cells (Dayton, Ohio) 2 30805989
2017 Identification of Mouse piRNA Pathway Components Using Anti-MIWI2 Antibodies. Methods in molecular biology (Clifton, N.J.) 2 27734358
2025 Somatic Miwi2 modulates mitochondrial function in airway multiciliated cells and exacerbates influenza pathogenesis. iScience 1 40241756
2025 A genetic variant in the 3'-UTR of PIWIL4 confers risk for extreme phenotypes of male infertility by altering miR-215 and miR-136 binding affinity. Human reproduction (Oxford, England) 1 40499151
2025 piR-43452 suppresses bladder cancer progression and enhances gemcitabine sensitivity via GTSF1/PIWIL4-mediated LRP1 mRNA destabilization. Translational oncology 1 41344056
2025 Functional Investigation of a Novel PIWIL4 Mutation in Nonobstructive Azoospermia During the First Wave of Spermatogenesis. Biomolecules 0 40001600
2011 [Identification and expression analysis of Macaca mulatta piwil4 gene]. Yi chuan = Hereditas 0 21482527

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