Affinage

YTHDF3

YTH domain-containing family protein 3 · UniProt Q7Z739

Audit flag: ungrounded claim
Length
585 aa
Mass
63.9 kDa
Annotated
2026-06-11
86 papers in source corpus 38 papers cited in narrative 40 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

YTHDF3 is a predominantly cytoplasmic reader of methylated RNA that integrates m6A-modified mRNA metabolism together with YTHDF1 and YTHDF2, simultaneously promoting protein synthesis and accelerating decay of distinct target transcripts (PMID:28106072). On the translational arm, YTHDF3 binds m6A sites—frequently in the 5' UTR or around the stop codon—and recruits translation initiation machinery including eIF3A, eIF4B, and the bridging factor eIF2AK2, with cofactors PABP1 and eIF4G2, to boost output of targets such as FOXO3, Ccnd1, CTNNB1, LOXL3, PRDX3, and Notch2 (PMID:30591559, PMID:36195598, PMID:36324258, PMID:35708211, PMID:35112553, PMID:39924078). On the decay arm, it destabilizes m6A-marked transcripts including SOX9, XRCC1, and HSPA13, in the latter case acting through liquid-liquid phase separation to recruit the decay factor DDX6 (PMID:38811341, PMID:40490202). Its reader activity extends beyond m6A: YTHDF3 recognizes m1A-modified mRNAs (IGF1R, TOPBP1, DSN1) to control their stability (PMID:32194978, PMID:41803797), and in genomic DNA it binds N6-methyladenine (6mA) and recruits the ALKBH1 demethylase to remove 6mA from double-stranded DNA (PMID:40715766). YTHDF3 abundance and activity are tuned post-translationally by ZDHHC20-mediated S-palmitoylation at Cys474, which blocks chaperone-mediated autophagic degradation, and by AARS2-dependent lactylation that antagonizes ubiquitin-mediated turnover (PMID:38821916, PMID:41621475). Through these activities YTHDF3 governs diverse physiological programs including autophagy (PMID:36195598), hematopoietic stem cell reconstitution (PMID:35112553), antiviral and innate immune signaling (PMID:30591559, PMID:32053707), DNA damage repair (PMID:41881836), and cardiac stress remodeling, where it controls stress-induced protein synthesis and cardiomyocyte size (PMID:40216557).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2017 High

    Established that YTHDF3 does not act alone but functions within the YTHDF reader family to coordinate the fate of m6A-modified mRNAs, resolving whether the three paralogs are redundant or integrated.

    Evidence Single and triple YTHDF knockouts with polysome profiling, mRNA stability assays, and m6A-seq

    PMID:28106072

    Open questions at the time
    • Did not define target-level specificity distinguishing the three readers
    • Did not identify the recruited effector machinery for translation versus decay
  2. 2018 High

    Showed YTHDF3 can act independently of m6A for at least one target, binding the FOXO3 translation initiation region via both its YTH and P/Q/N-rich domains to suppress interferon-stimulated genes.

    Evidence Reciprocal Co-IP, RIP, domain-deletion mutagenesis, YTHDF3 knockout mice, viral infection assays

    PMID:30591559

    Open questions at the time
    • Mechanism by which the P/Q/N-rich domain contributes to RNA binding not structurally defined
    • Whether m6A-independent binding generalizes beyond FOXO3 unknown
  3. 2020 High

    Broadened the reader repertoire by demonstrating YTHDF3 reads m1A as well as m6A, coupling m1A recognition of IGF1R mRNA to decay and adding a second modification mark to its functional scope.

    Evidence Mass-spec identification of m1A readers, iCLIP-seq, m1A-seq, RIP, mRNA stability and trophoblast invasion assays

    PMID:32194978

    Open questions at the time
    • Structural basis distinguishing m1A from m6A recognition not resolved
    • Whether m1A reading recruits the same decay machinery as m6A unknown
  4. 2020 High

    Defined cancer-relevant translational targets and an autoregulatory loop, showing YTHDF3 enhances translation of metastasis genes and binds m6A in its own 5' UTR to drive cap-independent self-translation.

    Evidence Overexpression/knockdown, polysome profiling, RIP, MeRIP-seq, in vivo brain metastasis models, reporter assays

    PMID:33125861

    Open questions at the time
    • Trigger for cap-independent autoregulation in physiology unclear
    • Initiation factors for these specific targets not yet mapped
  5. 2020 High

    Identified YTHDF3 as an antiviral restriction factor incorporated into HIV virions and a target of HIV protease cleavage, linking the reader to host-pathogen conflict.

    Evidence YTHDF3 knockout CD4+ T cells, HIV infection assays, mass spectrometry of virion proteins, protease inhibitor treatment

    PMID:32053707

    Open questions at the time
    • Molecular mechanism restricting reverse transcription not defined
    • Whether RNA-reading activity is required for restriction unclear
  6. 2021 Medium

    Placed YTHDF3 within innate immune signaling as a positive regulator of type I IFN JAK/STAT, and showed it is cleaved early by enterovirus 2A proteases.

    Evidence YTHDF depletion, viral infection, JAK/STAT inhibition, type I/II IFN treatment, ISG induction

    PMID:33849973

    Open questions at the time
    • Direct RNA targets mediating JAK/STAT enhancement not identified
    • Reconciliation with FOXO3-mediated ISG suppression not addressed
  7. 2022 High

    Identified the specific translation-initiation effectors recruited by YTHDF3—eIF3A, eIF4B, and bridging factor eIF2AK2—mechanistically explaining how it activates translation of m6A-marked targets across autophagy, cancer, and stem-cell contexts.

    Evidence Co-IP of YTHDF3/eIF3A/eIF2AK2/eIF4B complexes, MeRIP-seq, RIP, polysome profiling, CRISPR-Cas13b epitranscriptome editing, KO mouse rescue across multiple studies

    PMID:35110680 PMID:35112553 PMID:35708211 PMID:35779442 PMID:36195598 PMID:36324258

    Open questions at the time
    • Determinants selecting which m6A transcripts route to translation versus decay not defined
    • Stoichiometry and order of initiation factor recruitment unclear
  8. 2022 Low

    Provided a structural rationale for m6A recognition, modeling an aromatic cage in the YTH domain that anchors the methyl group and excludes water.

    Evidence All-atom molecular dynamics simulations and binding free-energy calculations

    PMID:35639481

    Open questions at the time
    • Computational only without experimental mutagenesis validation in this work
    • Does not address m1A or 6mA recognition modes
  9. 2022 Medium

    Demonstrated reciprocal stabilization of YTHDF3 protein by a downstream metabolic target, revealing the reader is itself regulated by ubiquitin-mediated turnover within feedback loops.

    Evidence MeRIP, Co-IP, ubiquitination assays, metabolomics, Ythdf3-/- mouse model

    PMID:36471428

    Open questions at the time
    • E3 ligase mediating YTHDF3 ubiquitination not identified
    • Direct versus indirect role of EFTUD2 unclear
  10. 2024 High

    Established post-translational control of YTHDF3 stability through ZDHHC20-mediated S-palmitoylation at Cys474, which blocks chaperone-mediated autophagic degradation and is druggable by competitive peptide.

    Evidence KPC mouse model, palmitoylation assays, Cys474 mutagenesis, CMA assays, competitive peptide, MYC mRNA stability assays

    PMID:38821916

    Open questions at the time
    • Whether palmitoylation alters RNA-binding or only stability unclear
    • Signals regulating ZDHHC20 activity on YTHDF3 unknown
  11. 2024 Medium

    Added lactylation as a second stabilizing post-translational mark, installed in an AARS2-dependent manner and antagonizing ubiquitin-mediated degradation.

    Evidence Lactylation assays, lactylation-deficient mutant, ubiquitination assays, MeRIP, RIP, mRNA stability, xenografts

    PMID:41621475

    Open questions at the time
    • Lactylation site(s) on YTHDF3 not defined
    • Interplay between lactylation and palmitoylation unresolved
  12. 2025 Medium

    Revealed a phase-separation-dependent decay mechanism in which YTHDF3 condensates recruit DDX6 to degrade target mRNA, mechanistically linking biophysical condensation to its decay arm.

    Evidence Phase-separation assays, phase-separation-disrupting mutant, HSPA13 mRNA degradation, DDX6 recruitment, in vivo tumor models

    PMID:38811341

    Open questions at the time
    • Whether condensation is required for all decay targets unknown
    • Domain driving phase separation not finely mapped
  13. 2025 High

    Extended YTHDF3 function from RNA to DNA, showing it reads genomic 6mA and recruits ALKBH1 to demethylate double-stranded DNA, a substrate conformation ALKBH1 handles poorly alone.

    Evidence In vitro biochemical binding and demethylation assays across DNA conformations, YTHDF3-ALKBH1 Co-IP, genomic 6mA quantification

    PMID:40715766

    Open questions at the time
    • Genomic loci and biological consequences of 6mA reading not mapped
    • Whether nuclear localization for this function is regulated unclear
  14. 2025 Low

    Defined a nuclear, splicing-regulatory role in cardiomyocytes where YTHDF3 partners with DDX5 and HNRNPU, challenging the strictly cytoplasmic reader model.

    Evidence Nuclear/cytoplasmic fractionation, Co-IP/LC-MS-MS, alternative splicing analysis, knockdown/overexpression (preprint)

    Open questions at the time
    • Preprint not yet peer-reviewed
    • Novel nuclear localization claim awaits independent replication
    • Whether splicing role depends on m6A reading unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved what molecular features partition individual methylated transcripts between YTHDF3-driven translation versus decay, and how its newly described nuclear functions (splicing, 6mA/DNA reading) are coordinated with its cytoplasmic reader activity.
  • No unifying code distinguishing translation- versus decay-fated targets
  • Spatial regulation between cytoplasmic and nuclear pools undefined
  • Functional hierarchy among m6A, m1A, and 6mA reading not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 6 GO:0045182 translation regulator activity 5 GO:0140110 transcription regulator activity 4 GO:0003677 DNA binding 1
Localization
GO:0005829 cytosol 3 GO:0005634 nucleus 2
Pathway
R-HSA-168256 Immune System 5 R-HSA-392499 Metabolism of proteins 5 R-HSA-8953854 Metabolism of RNA 4 R-HSA-73894 DNA Repair 2 R-HSA-9612973 Autophagy 1
Partners
ALKBH1DDX6EIF2AK2EIF3AEIF4BYTHDF1YTHDF2ZDHHC20

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2017 YTHDF3 promotes protein synthesis in synergy with YTHDF1 and affects m6A-modified mRNA decay mediated through YTHDF2; cells deficient in all three YTHDF proteins show the most dramatic accumulation of m6A-modified transcripts, indicating cooperative and integrated cytoplasmic metabolism of m6A-modified mRNAs. Genetic depletion (single and triple knockouts), polysome profiling, mRNA stability assays, m6A-seq Cell Research High 28106072
2018 YTHDF3 suppresses interferon-stimulated gene (ISG) expression by promoting translation of the transcription co-repressor FOXO3 mRNA; YTHDF3 cooperates with cofactors PABP1 and eIF4G2 to promote FOXO3 translation by binding the translation initiation region of FOXO3 mRNA. Both the YTH and the P/Q/N-rich domains of YTHDF3 are required for FOXO3 RNA-binding capacity. Notably, METTL3-mediated m6A modification was NOT required for this specific interaction. Co-immunoprecipitation, RNA immunoprecipitation, YTHDF3 knockout mice, domain-deletion mutagenesis, viral infection assays PNAS High 30591559
2020 YTHDF3 enhances translation of m6A-enriched transcripts ST6GALNAC5, GJA1, and EGFR to promote breast cancer brain metastasis. Additionally, YTHDF3 undergoes cap-independent autoregulation of its own translation by binding m6A residues within its own 5' UTR. YTHDF3 overexpression/knockdown, polysome profiling, RIP, MeRIP-seq, in vivo brain metastasis models, reporter assays Cancer Cell High 33125861
2020 YTHDF3 acts as an m1A (N1-methyladenosine) reader protein in addition to m6A; it binds m1A-modified IGF1R mRNA and promotes its degradation, thereby inhibiting IGF1R protein expression and downstream MMP9 signaling, reducing trophoblast invasion and migration. Mass spectrometry identification of m1A readers, iCLIP-seq, m1A-seq, RNA immunoprecipitation, mRNA stability assays, trophoblast invasion/migration assays Cell Discovery High 32194978
2020 HIV protease cleaves virion-incorporated YTHDF3 protein (identified by mass spectrometry); YTHDF3 is incorporated into HIV particles in a nucleocapsid-dependent manner and acts as a restriction factor limiting infection at the step of reverse transcription. HIV protease inhibitors block YTHDF3 cleavage. YTHDF3 knockout in CD4+ T cells, HIV infection assays, mass spectrometry of virion proteins, HIV protease inhibitor treatment PLoS Pathogens High 32053707
2021 Enterovirus 2A proteases cleave YTHDF3 (and other YTHDF proteins) very early during infection. YTHDF3 acts as a positive regulator of type I interferon-mediated JAK/STAT signaling; YTHDF3 depletion impaired JAK/STAT signaling in cells treated with type I (but not type II) IFN, and enhanced viral translation/replication specifically in cells mounting innate immune responses. YTHDF protein depletion, viral infection assays, JAK/STAT inhibition, type I/II IFN treatment, ISG induction measurement mBio Medium 33849973
2022 YTHDF3 promotes autophagy induction by recognizing m6A modification sites around the stop codon of FOXO3 mRNA and recruiting eIF3a and eIF4B to facilitate FOXO3 translation upon nutrient deficiency; METTL3 depletion abolishes this YTHDF3-mediated autophagy flux. YTHDF3 and METTL3 depletion, autophagosome formation assays, lysosomal degradation assays, RIP, MeRIP-seq, eIF3a/eIF4B co-immunoprecipitation Nature Communications High 36195598
2022 YTHDF3 facilitates translation of m6A-modified CTNNB1 (β-catenin) mRNA in ocular melanoma, promoting cancer stem-like cell properties and tumor growth. YTHDF3 knockdown/overexpression, MeRIP-seq, RIP, polysome profiling, in vitro and in vivo tumor models Oncogene Medium 35110680
2022 YTHDF3 promotes PFKL mRNA stability and expression via m6A modification, enhancing aerobic glycolysis in hepatocellular carcinoma; PFKL reciprocally stabilizes YTHDF3 protein by inhibiting its ubiquitination via EFTUD2 (a spliceosome subunit), forming a positive feedback loop. MeRIP assay, co-immunoprecipitation, immunofluorescence, ubiquitination assays, metabolomics, Ythdf3-/- mouse model Journal of Experimental & Clinical Cancer Research Medium 36471428
2022 YTHDF3 recognizes m6A-modified PRDX3 mRNA and promotes its translation in an m6A-dependent manner; YTHDF3 knockdown (but not YTHDF1/2 knockdown) suppressed PRDX3 expression, demonstrating specificity among YTHDF family members for this target. RNA pull-down/mass spectrometry, YTHDF1/2/3 knockdown comparison, translation assays, RIP Redox Biology Medium 35779442
2022 YTHDF3 recognizes m6A binding sites on LOXL3 mRNA and enhances its translation by enriching eIF3A on the LOXL3 transcript, increasing LOXL3 protein without affecting mRNA level; this was confirmed by CRISPR-Cas13b-based epitranscriptome engineering. RNA-seq, MeRIP-seq, RIP-seq, mass spectrometry, CRISPR-Cas13b epitranscriptome editing, RIP-qPCR, MeRIP-qPCR, eIF3A co-immunoprecipitation Clinical and Translational Medicine High 36324258
2022 YTHDF3 facilitates translation of m6A-modified genes in oxaliplatin-resistant colorectal cancer by recognizing 5' UTR m6A and recruiting eIF3A; eIF2AK2 bridges YTHDF3 and eIF3A, enhancing the stability of the YTHDF3/eIF3A translational complex. RIP, MeRIP, Co-immunoprecipitation of YTHDF3/eIF2AK2/eIF3A complex, translation assays ACS Chemical Biology Medium 35708211
2022 YTHDF3 modulates hematopoietic stem cell reconstitution capacity by transmitting m6A RNA methylation on the 5' UTR of Ccnd1 (Cyclin D1) mRNA to promote its translation; enforced Ccnd1 expression completely rescued Ythdf3-/- HSC defects. Ythdf3-/- and Mettl3-/- mouse models, bone marrow reconstitution assays, translational defect analysis, rescue experiments with Ccnd1 overexpression Haematologica High 35112553
2022 METTL3 methylates MCU mRNA at three m6A residues in the 3'-UTR; YTHDF3 associates with methylated MCU mRNA and promotes its translation, increasing MCU protein expression and contributing to HCMV-induced vascular endothelial apoptosis. MeRIP-qPCR, RIP, METTL3/YTHDF3 knockdown/overexpression, MCU translation assays Frontiers in Microbiology Medium 35359726
2022 YTHDF3 promotes RAD51D mRNA N6-methyladenosine modification in an HNF1α-dependent manner and promotes RAD51D translation, conferring radioresistance in cervical cancer; HNF1α upregulates YTHDF3 transcription. HNF1α/YTHDF3 knockdown/overexpression, m6A modification analysis, translational assays, in vitro and in vivo irradiation resistance assays FEBS Journal Medium 36380687
2022 YTHDF3 depletion in ESCs results in loss of pluripotency with accelerated germ layer differentiation; knockdown of YTHDF3 accelerated cardiomyocyte differentiation, whereas YTHDF1 depletion impaired it. YTHDF3 appears to modulate differentiation partially through suppression of YTHDF1. YTHDF1/YTHDF3 knockdown in ESCs, transcriptomic analysis, cardiomyocyte differentiation assays, marker gene expression RNA Biology Medium 33295243
2022 Molecular dynamics simulation studies reveal that the YTH domain of YTHDF3 recognizes m6A via an aromatic cage in which Trp492 anchors the methyl group and Trp438/Trp497 provide π-π stacking; m6A methylation enhances hydrophobicity, excluding water from the aromatic cage and stabilizing the complex via induced-fit and conformation selection mechanisms. All-atom molecular dynamics simulations, binding free energy calculations, hydrogen bond analysis Proteins Low 35639481
2024 ZDHHC20-mediated S-palmitoylation of YTHDF3 at Cys474 inhibits chaperone-mediated autophagic degradation of YTHDF3, leading to its accumulation and stabilization of MYC mRNA; a YTHDF3-derived competitive peptide inhibiting this palmitoylation downregulates MYC and inhibits pancreatic cancer progression. KPC mouse model, palmitoylation assays, Cys474 mutagenesis, chaperone-mediated autophagy assays, competitive peptide design, MYC mRNA stability assays Nature Communications High 38821916
2024 YTHDF3 promotes degradation of SPOP and NKX3.1 mRNAs and stabilizes TWIST1 and SNAI2 mRNAs in an m6A-dependent manner in castration-resistant prostate cancer; melatonin competes with m6A to occupy the m6A-binding cage of YTHDF3, inhibiting its target mRNA regulation. YTHDF3 overexpression/knockdown, m6A-dependent mRNA stability assays, melatonin competition binding assays, in vitro and in vivo tumor models Journal of Pineal Research Medium 39143673
2024 YTHDF3 undergoes AARS2-dependent lactylation, which stabilizes the protein by antagonizing ubiquitin-mediated degradation; lactylated YTHDF3 enhances m6A-dependent recognition and decay of KDM6B mRNA, suppressing CDKN1A transcription via impaired H3K27me3 demethylation and promoting cisplatin resistance in bladder cancer. Lactylation assays, YTHDF3 lactylation-deficient mutant, ubiquitination assays, MeRIP, RIP, KDM6B mRNA stability assays, xenograft models Cancer Letters Medium 41621475
2024 METTL3-mediated m6A modification of SOX4 mRNA (in the CDS region) is recognized by YTHDF3, which regulates SOX4 mRNA stability; YTHDF3 knockdown reduced SOX4 mRNA stability and compromised osteoblast differentiation downstream of METTL3. MeRIP-seq, RNA-seq, RIP assay, METTL3/YTHDF3 knockdown, osteoblast differentiation assays, in vivo OVX mouse model Cellular Signalling Medium 38195035
2024 FTO demethylation of PDK1 mRNA prevents YTHDF3 from recognizing and binding to m6A sites on PDK1 mRNA, thus inhibiting PDK1 mRNA degradation; this axis links hypoxia-driven FTO upregulation to PDK1/AKT/STAT3/PD-L1 immunosuppression in breast cancer. MeRIP-seq, RIP, PDK1 mRNA stability assays, FTO/YTHDF3 knockdown/overexpression, in vivo mouse models Journal of Advanced Research Medium 39701379
2025 YTHDF3 recognizes DNA N6-methyladenine (6mA) in genomic DNA (including double-stranded DNA) and recruits ALKBH1 demethylase to 6mA sites in genomic DNA, facilitating ALKBH1-mediated removal of 6mA in dsDNA—a conformation for which ALKBH1 alone has limited activity. Biochemical binding assays with 6mA-modified DNA, Co-immunoprecipitation of YTHDF3-ALKBH1, 6mA demethylation activity assays with various DNA conformations, genomic 6mA quantification The EMBO Journal High 40715766
2025 YTHDF3 promotes cardiac stress-induced protein synthesis and controls cardiomyocyte size; cardiomyocyte-specific deletion of YTHDF3 in mice attenuates pathological cardiac remodeling following pressure overload injury. Cardiomyocyte-specific YTHDF3 conditional knockout mice, pressure overload (transverse aortic constriction) model, global protein synthesis measurement RNA Medium 40216557
2025 YTHDF3 interacts with BTG2 and is involved in the decay of Cbln1 mRNA; increased YTHDF3 levels in hippocampus of prenatal hypoxia offspring lead to Cbln1 downregulation, contributing to abnormal synaptic function and cognitive impairment. Co-immunoprecipitation of YTHDF3-BTG2, mRNA decay assays, hippocampal YTHDF3 measurement, Cbln1 expression analysis iScience Medium 38205248
2025 YTHDF3 phase separation characteristics enable it to suppress ccRCC malignancy and PD-L1-mediated immune evasion by recruiting DDX6 to degrade HSPA13 mRNA; a YTHDF3 mutant disrupting phase separation abolishes these functions. Phase separation assays, YTHDF3 mutant disrupting phase separation, HSPA13 mRNA degradation assays, DDX6 recruitment assays, in vivo tumor models with CD8+ T cell measurement Cancer Science Medium 38811341
2025 YTHDF3 binds to m6A-modified STAT3 mRNA to enhance its stability and transcription efficiency; this YTHDF3-STAT3 axis represses IRF7 transcription and IFN-α production, suppressing type I ISG responses and antiviral immunity in HPV-driven cervical cancer. CRISPR/Cas9 YTHDF3-/- cells and Ythdf3-/- mice, RIP, MeRIP, STAT3 mRNA stability assays, ISG induction measurement, in vivo xenograft immune cell profiling Cell Death & Disease Medium 41453852
2025 YTHDF3 promotes FLCN mRNA stability via m6A methylation; FLCN in turn binds cPLA2 to increase its activity and regulate lysosomal membrane permeabilization in cardiac fibroblasts, with YTHDF3 overexpression reducing collagen production and improving cardiac fibrosis in TAC mice. MeRIP, mRNA stability assays, FLCN/cPLA2 Co-IP, TAC mouse model, YTHDF3/FLCN overexpression in vivo Acta Pharmacologica Sinica Medium 39806064
2025 YTHDF3 promotes YTHDF3-mediated mRNA decay of SOX9; loss of Ythdf3 in mice leads to impaired SOX9 mRNA decay, causing cardiac hypertrophy, myopathy, and intellectual abnormalities resembling Danon disease; AAV-shRNA targeting Sox9 rescued these phenotypes. Ythdf3-/- mouse model, Sox9 mRNA decay assays, AAV-shRNA rescue experiments, cardiac and neurological phenotyping bioRxivpreprint Medium
2025 In cardiomyocytes, Ythdf3 localizes to the nucleus (contrary to its predominantly cytoplasmic localization elsewhere) and interacts with splicing proteins DDX5 and HNRNPU to regulate alternative splicing, including splicing of CaMKIIδ isoforms; Ythdf3 knockdown increases CaMKIIδA and CaMKIIδC isoforms while decreasing CaMKIIδ9. Nuclear/cytoplasmic fractionation with imaging, Co-immunoprecipitation coupled with LC-MS/MS, alternative splicing analysis, Ythdf3 knockdown/overexpression, electron microscopy bioRxivpreprint Low
2025 YTHDF3 promotes m6A-dependent stabilization of Wnt3 mRNA in glioma in synergy with circ_EPHB4; YTHDF3 alone extends the half-life of Wnt3 mRNA in an m6A-dependent manner, and simultaneous knockdown of both circ_EPHB4 and YTHDF3 reduces Wnt3 mRNA expression more than either alone. RIP, RNA stability assays, circ_EPHB4/YTHDF3 knockdown, gene co-expression rescue, in vivo tumor models Journal of Southern Medical University Low 41311073
2025 TRMT6 installs m1A marks on TOPBP1 and DSN1 mRNAs; YTHDF3 reads these m1A modifications and stabilizes these cell-cycle mRNAs, promoting lung squamous cell carcinoma proliferation; a single m1A site in each mRNA is sufficient to boost their expression. m1A-seq, RIP, dCasRx-TRMT6 site-specific m1A deposition, YTHDF3/TRMT6 knockdown, in vitro and in vivo proliferation assays NPJ Precision Oncology Medium 41803797
2025 YTHDF3 depletion in GC cell lines impairs cytoskeleton organization, cell migration, metastasis, and mitotic spindle orientation, leading to increased paclitaxel sensitivity; EZRIN (EZR) mRNA was identified as a direct YTHDF3 target via RNA immunoprecipitation, with m6A sites mapped by SELECT method. CRISPR-Cas9 YTHDF3 knockout, RIP, SELECT method for m6A mapping on EZR, migration/invasion/spindle orientation assays, paclitaxel sensitivity assays Gastric Cancer Medium 40366509
2025 YTHDF3 promotes translation of Notch2 mRNA in an m6A-dependent manner by recruiting eIF4B; YTHDF3 binds m6A-modified Notch2 mRNA and its knockdown reduces Notch2 protein levels and EMT. RIP, MeRIP, eIF4B Co-immunoprecipitation, Notch2 translation assays, in vitro/in vivo EMT and metastasis models Cancer Letters Medium 39924078
2025 Histone lactylation promotes YTHDF3 expression, and YTHDF3 in turn promotes m6A-dependent translation of PRDX3 mRNA; reduced YTHDF3 from sevoflurane exposure decreases PRDX3, activating NLRP3 inflammasome-mediated pyroptosis in microglia. ChIP assay for histone lactylation at YTHDF3 promoter, RIP for YTHDF3-PRDX3 mRNA interaction, YTHDF3 overexpression rescue, NLRP3/caspase-1 activity assays International Immunopharmacology Medium 40022822
2025 YTHDF3 promotes degradation of XRCC1 mRNA in an m6A-dependent manner in the rostral ventrolateral medulla; YTHDF3 knockdown increased XRCC1 expression, facilitated DNA damage repair in neurons, reduced neuronal apoptosis, and lowered blood pressure in spontaneously hypertensive rats. YTHDF3 knockdown in RVLM of SHRs, m6A-dependent mRNA stability assays for XRCC1, neuronal excitability and sympathetic tone measurement, blood pressure recording, in vitro rescue with XRCC1 Free Radical Biology & Medicine Medium 40490202
2026 YTHDF3 directly recognizes BRCA1, RAD51, RIF1, and 53BP1 mRNAs via m6A binding sites and promotes their translation, facilitating homologous recombination and NHEJ DNA repair in glioblastoma, contributing to temozolomide resistance; TMZ treatment increases m6A modification levels to facilitate this YTHDF3-mediated DDR. YTHDF3 and METTL3 knockdown, m6A-modified DDR gene mRNA translation assays, DNA repair assays (HR and NHEJ), PDC models Cancer Letters Medium 41881836
2025 YTHDF3 binds m6A-modified SOCS1 mRNA to enhance both its stability and translation, upregulating SOCS1 expression and thereby inhibiting the JAK1/STAT3 pathway in trophoblast cells, promoting preeclampsia pathogenesis. YTHDF3 knockdown in trophoblast cells, MeRIP, RIP, mRNA stability assays, JAK1/STAT3 pathway activity measurement The Journal of Gene Medicine Low 41287146
2025 YTHDF3 accelerates degradation of key TLR4 pathway mRNAs (Cd36, Irak1, Tab1/2, Tirap) to suppress macrophage activation; Ythdf3 knockdown inhibits their degradation and enhances p38 phosphorylation, LPS-induced pro-inflammatory cytokine production, phagocytosis, and tumor-killing activity. shRNA Ythdf3 knockdown in RAW264.7 cells, mRNA stability analysis, p38 phosphorylation immunoblotting, cytokine ELISA, phagocytosis and tumor co-culture assays Sichuan University Journal Medium 40964113
2026 YTHDF3 maintains SIRT2 mRNA stability via m6A binding, facilitating SIRT2-mediated deacetylation of FOXO1 and reducing FOXO1 protein stability, thereby promoting Ang II-induced VSMC apoptosis and inflammation in abdominal aortic aneurysm. MeRIP-qPCR, RIP, mRNA stability assay, cycloheximide chase, co-immunoprecipitation, YTHDF3 knockdown in VSMCs Korean Circulation Journal Low 41972268

Source papers

Stage 0 corpus · 86 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 YTHDF3 facilitates translation and decay of N6-methyladenosine-modified RNA. Cell research 1498 28106072
2019 Long noncoding RNA GAS5 inhibits progression of colorectal cancer by interacting with and triggering YAP phosphorylation and degradation and is negatively regulated by the m6A reader YTHDF3. Molecular cancer 506 31619268
2020 YTHDF3 Induces the Translation of m6A-Enriched Gene Transcripts to Promote Breast Cancer Brain Metastasis. Cancer cell 336 33125861
2018 RNA-binding protein YTHDF3 suppresses interferon-dependent antiviral responses by promoting FOXO3 translation. Proceedings of the National Academy of Sciences of the United States of America 149 30591559
2022 Autophagy induction promoted by m6A reader YTHDF3 through translation upregulation of FOXO3 mRNA. Nature communications 97 36195598
2020 circ_KIAA1429 accelerates hepatocellular carcinoma advancement through the mechanism of m6A-YTHDF3-Zeb1. Life sciences 97 32653519
2022 The m6A reader YTHDF3-mediated PRDX3 translation alleviates liver fibrosis. Redox biology 74 35779442
2020 Cytoplasmic m1A reader YTHDF3 inhibits trophoblast invasion by downregulation of m1A-methylated IGF1R. Cell discovery 73 32194978
2022 A reciprocal feedback between N6-methyladenosine reader YTHDF3 and lncRNA DICER1-AS1 promotes glycolysis of pancreatic cancer through inhibiting maturation of miR-5586-5p. Journal of experimental & clinical cancer research : CR 66 35183226
2022 The m6A reading protein YTHDF3 potentiates tumorigenicity of cancer stem-like cells in ocular melanoma through facilitating CTNNB1 translation. Oncogene 59 35110680
2022 A functional loop between YTH domain family protein YTHDF3 mediated m6A modification and phosphofructokinase PFKL in glycolysis of hepatocellular carcinoma. Journal of experimental & clinical cancer research : CR 58 36471428
2024 ZDHHC20-mediated S-palmitoylation of YTHDF3 stabilizes MYC mRNA to promote pancreatic cancer progression. Nature communications 57 38821916
2019 m6A RNA modification and its writer/reader VIRMA/YTHDF3 in testicular germ cell tumors: a role in seminoma phenotype maintenance. Journal of translational medicine 51 30866959
2022 YTHDF3 facilitates triple-negative breast cancer progression and metastasis by stabilizing ZEB1 mRNA in an m6A-dependent manner. Annals of translational medicine 49 35282088
2022 N1-Methyladenosine (m1A) Regulation Associated With the Pathogenesis of Abdominal Aortic Aneurysm Through YTHDF3 Modulating Macrophage Polarization. Frontiers in cardiovascular medicine 46 35620523
2020 Differential roles of YTHDF1 and YTHDF3 in embryonic stem cell-derived cardiomyocyte differentiation. RNA biology 44 33295243
2020 HIV protease cleaves the antiviral m6A reader protein YTHDF3 in the viral particle. PLoS pathogens 42 32053707
2022 YTHDF3 Facilitates eIF2AK2 and eIF3A Recruitment on mRNAs to Regulate Translational Processes in Oxaliplatin-Resistant Colorectal Cancer. ACS chemical biology 37 35708211
2021 KDM5B promotes self-renewal of hepatocellular carcinoma cells through the microRNA-448-mediated YTHDF3/ITGA6 axis. Journal of cellular and molecular medicine 35 33829656
2022 Vitamin D3 Suppresses Human Cytomegalovirus-Induced Vascular Endothelial Apoptosis via Rectification of Paradoxical m6A Modification of Mitochondrial Calcium Uniporter mRNA, Which Is Regulated by METTL3 and YTHDF3. Frontiers in microbiology 34 35359726
2022 N6-methyladenosine reader YTHDF3 regulates melanoma metastasis via its 'executor'LOXL3. Clinical and translational medicine 34 36324258
2022 YTHDF3 mediates HNF1α regulation of cervical cancer radio-resistance by promoting RAD51D translation in an m6A-dependent manner. The FEBS journal 32 36380687
2022 YTHDF3 modulates hematopoietic stem cells by recognizing RNA m6A modification on Ccnd1. Haematologica 29 35112553
2024 FTO activates PD-L1 promotes immunosuppression in breast cancer via the m6A/YTHDF3/PDK1 axis under hypoxic conditions. Journal of advanced research 28 39701379
2021 Enterovirus 2Apro Cleavage of the YTHDF m6A Readers Implicates YTHDF3 as a Mediator of Type I Interferon-Driven JAK/STAT Signaling. mBio 28 33849973
2024 The inhibition of YTHDF3/m6A/LRP6 reprograms fatty acid metabolism and suppresses lymph node metastasis in cervical cancer. International journal of biological sciences 26 38250152
2024 METTL3-mediated m6A modification of SOX4 regulates osteoblast proliferation and differentiation via YTHDF3 recognition. Cellular signalling 22 38195035
2022 N6-methyladenosine reader YTHDF3 contributes to the aerobic glycolysis of osteosarcoma through stabilizing PGK1 stability. Journal of cancer research and clinical oncology 20 36171455
2023 m6 A reader YTHDF3 triggers the progression of hepatocellular carcinoma through the YTHDF3/m6 A-EGFR/STAT3 axis and EMT. Molecular carcinogenesis 18 37449789
2024 YTHDF3 phase separation regulates HSPA13-dependent clear cell renal cell carcinoma development and immune evasion. Cancer science 17 38811341
2025 The YTHDF3-DT/miR-301a-3p /INHBA axis attenuates autophagy-dependent ferroptosis in lung adenocarcinoma. Cancer letters 14 39892700
2024 YTHDF3 Regulates the Degradation and Stability of m6A-Enriched Transcripts to Facilitate the Progression of Castration-Resistant Prostate Cancer. Journal of pineal research 13 39143673
2024 YTHDF3-induced degradation of P4HA2 mRNA inhibits glycolysis in papillary thyroid cancer through Hippo signaling pathway. International journal of biological macromolecules 13 39725111
2022 Epitranscriptomic turbo for autophagy boost: m6A reader YTHDF3. Autophagy 13 36374269
2024 N6-methyladenosine reader YTHDF3-mediated zinc finger protein 41 inhibits hepatocellular carcinoma progression by transcriptional repression of Snail. MedComm 11 39473907
2022 YTHDF3 Is Involved in the Diapause Process of Bivoltine Bombyx mori Strains by Regulating the Expression of Cyp307a1 and Cyp18a1 Genes in the Ecdysone Synthesis Pathway. Biomolecules 11 36009021
2025 YTHDF3 drives tumor growth and metastasis by recruiting eIF4B to promote Notch2 translation in breast cancer. Cancer letters 9 39924078
2025 Histone lactylation protects against sevoflurane-induced cognitive impairment by regulating YTHDF3/PRDX3 mediated microglial pyroptosis in neonatal mice. International immunopharmacology 9 40022822
2025 YTHDF3 regulates IL32 mRNA stability to promote osteogenic differentiation of bone mesenchymal stem cells in ankylosing spondylitis. Journal of translational medicine 9 40448194
2024 Knockdown of YAP1 Reduces YTHDF3 to Stabilize SMAD7 and thus Inhibit Bladder Cancer Stem Cell Stemness. Discovery medicine 8 39054719
2024 YTHDF3-mediated m6A modification of NKD1 regulates hepatocellular carcinoma invasion and metastasis by activating the WNT/β-catenin signaling axis. Experimental cell research 8 39127439
2024 YTHDF3 suppresses declines in corneal epithelial wound healing through upregulating the Wnt/β-catenin signaling pathway and THBS2 expression in diabetic corneas. International journal of biological macromolecules 7 39626342
2023 YTHDF3 Modulates EGFR/ATK/ERK/p21 Signaling Axis to Promote Cancer Progression and Osimertinib Resistance of Glioblastoma Cells. Anticancer research 7 38030188
2023 YTHDF3 modulates the Cbln1 level by recruiting BTG2 and is implicated in the impaired cognition of prenatal hypoxia offspring. iScience 7 38205248
2024 Overexpression of YTHDF3 increases the specific productivity of the recombinant protein in CHO cells by promoting the translation process. Biotechnology journal 6 38651251
2022 Specific recognition between YTHDF3 and m6 A-modified RNA: An all-atom molecular dynamics simulation study. Proteins 6 35639481
2024 YTHDF3 modulates the progression of breast cancer cells by regulating FGF2 through m6A methylation. Frontiers in cell and developmental biology 5 39372951
2023 Overexpression of FTO inhibits excessive proliferation and promotes the apoptosis of human glomerular mesangial cells by alleviating FOXO6 m6A modification via YTHDF3-dependent mechanisms. Frontiers in pharmacology 5 37822879
2023 Celastrol suppresses human pancreatic cancer via m6A-YTHDF3-mediated downregulation of Claspin and Bcl-2. Discover oncology 5 38110764
2025 The m6A reader YTHDF3 promotes TNBC progression by regulating CENPI stabilization. Frontiers in oncology 4 40406242
2025 N6-methyladenosine reader YTHDF3-mediated CEBPA translation maintains genomic stability and stem cell function to prevent liver injury. Science China. Life sciences 4 40488955
2026 Lactylation enhances YTHDF3 stability to promote cisplatin resistance via m6A-dependent KDM6B decay in bladder cancer. Cancer letters 3 41621475
2025 The m6A-binding protein YTHDF3 modulates the cardiac response to stress. RNA (New York, N.Y.) 3 40216557
2025 The RNA-binding protein YTHDF3 affects gastric cancer cell migration and response to paclitaxel by regulating EZRIN. Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 3 40366509
2025 YTHDF3 recognizes DNA N6-methyladenine and recruits ALKBH1 for 6mA removal from genomic DNA. The EMBO journal 3 40715766
2025 CircZFR/YTHDF3 axis drives lymph node metastasis in cervical cancer via FASN translation. Molecular cancer 3 40841902
2025 YTHDF3-mediated FLCN/cPLA2 axis improves cardiac fibrosis via suppressing lysosomal function. Acta pharmacologica Sinica 2 39806064
2025 m6A reader YTHDF3 elicits hypertensive effects by degrading XRCC1 mRNA in the rostral ventrolateral medulla. Free radical biology & medicine 2 40490202
2025 METTL3/YTHDF3 m6A axis promotes ferroptosis in diabetic kidney disease by stabilizing TfR1. Journal of diabetes investigation 2 40492436
2025 Targeting the METTL3/YTHDF3/m6A/PGK1 axis to combat Choriocarcinoma progression. Archives of biochemistry and biophysics 2 40681032
2021 Mono-allelic loss of YTHDF3 and neurodevelopmental disorder: clinical features of four individuals with 8q12.3 deletions. Clinical genetics 2 34708403
2026 Epitranscriptomic regulation of NVP-BEZ235 resistance in ccRCC via the YTHDF3-SYNM regulatory pathway. Genes & genomics 1 41591631
2025 The m6A regulatory gene YTHDF3 alleviates acute pancreatitis by modulating CD45RA+ resting treg cells: A novel immunomodulatory biomarker. Medicine 1 40958316
2025 RNA m6A reader YTHDF3/ UBE2G2 m6A methylation/ ACSL4 ubiquitination axis facilitated cell ferroptosis to mediate benzene hematotoxicity and the protective effect of melatonin. Ecotoxicology and environmental safety 1 41125048
2025 YTHDF3 promotes breast cancer osteolytic bone metastasis by enhancing the translation of ZEB1 and SMAD5. Oncogenesis 1 41249131
2025 YTHDF3 Stabilizes the Expression of m6A-Mediated LRRC17 and Induces Osteoarthritic Chondrocyte Senescence by Activating the STAT1 Signaling. Geriatrics & gerontology international 1 41365291
2026 N6-methyladenosine reader YTHDF3-mediated Lcn2 mRNA stability promotes the hepatotoxicity of crizotinib. Toxicological sciences : an official journal of the Society of Toxicology 0 41183147
2026 METTL3-regulated m6A modification modulates autophagy of placental mesenchymal stem/stromal cell by YTHDF3-mediated degradation of LncRNA GAS5 in preeclampsia. Placenta 0 41679189
2026 The METTL14/YTHDF3 axis regulates EPSTI1-mediated osteogenic differentiation of human bone marrow mesenchymal stem cells. Tissue & cell 0 41690067
2026 TRMT6-directed m1A modification initiates lung squamous cell carcinoma via YTHDF3-stabilized cell cycle genes. NPJ precision oncology 0 41803297
2026 YTHDF3 facilitates DNA damage response by recognizing METTL3-mediated m6A modification to promote chemotherapy resistance in glioblastoma. Cancer letters 0 41881336
2026 YTHDF3 Hinders the Proliferation of Ang II-Induced Vascular Smooth Muscle Cells While Promoting Apoptosis and Inflammation in Abdominal Aortic Aneurysm via SIRT2/FOXO1. Korean circulation journal 0 41972268
2026 The m6A Reader YTHDF3 Promotes Glioma Progression by Regulating the m6A Modification of lncRNA-PAR5. Analytical cellular pathology (Amsterdam) 0 41992409
2026 The N6-methyladenosine (m6A) reader YTHDF3 increases PINK1/Parkin-mediated mitophagy by facilitating prohibitin 2 (PHB2) translation to promote retinal ganglion cell damage in diabetic retinopathy. Journal of neuropathology and experimental neurology 0 42024680
2026 YTHDF3 Mediates the Occurrence and Development of Breast Cancer by Regulating Glycolysis Through the mTOR-HIF1α-LHDA Axis. Journal of cellular and molecular medicine 0 42036761
2026 Melatonin Counteracts Mechanical Unloading-Induced Bone Loss Through YTHDF3-Mediated m6A Modification of Dapk2 mRNA. Journal of pineal research 0 42149012
2026 YTHDF3 Enhances Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells in Osteoporosis by Promoting TBX19 Expression. Cell proliferation 0 42235938
2026 Potential Relationship Between YTHDF3 and CFTR in Myocardial Ischemia-Reperfusion Injury. Journal of cellular and molecular medicine 0 42265766
2025 [YTHDF3 Regulates Macrophage Activation: Investigation of the Mechanisms Involved]. Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition 0 40964113
2025 YTHDF3 Promotes N6-Methyladenosine Modification of SOCS1 to Inhibit JAK1/STAT3 Pathway in the Pathogenesis of Preeclampsia. The journal of gene medicine 0 41287146
2025 [circ_EPHB4 synergizes with YTHDF3 to promote glioma progression via m6A-dependent stabilization of Wnt3]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 0 41311073
2025 YTHDF3-TRIM2-P53 axis promotes malignant progression in uveal melanoma (UVM). Cellular signalling 0 41391676
2025 YTHDF3 suppresses interferon-stimulated gene (ISG)-dependent antitumor immunity and promotes HPV carcinogenesis in cervical cancer. Cell death & disease 0 41453852
2025 YTHDF3 at the crossroads of the Epitranscriptome: Structure, networks, and disease roles. Cellular signalling 0 41674043
2024 YTHDF3 gene polymorphisms increase Wilms tumor risk in Chinese girls. Journal of Cancer 0 39440064
2024 YTHDF3 rs7464 A > G polymorphism increases Chinese neuroblastoma risk: A multiple-center case-control study. IUBMB life 0 39575986

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