Affinage

YTHDC1

YTH domain-containing protein 1 · UniProt Q96MU7

Length
727 aa
Mass
84.7 kDa
Annotated
2026-04-28
100 papers in source corpus 47 papers cited in narrative 47 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

YTHDC1 is a nuclear N6-methyladenosine (m6A) reader that orchestrates multiple co-transcriptional and post-transcriptional RNA processing events, including alternative splicing, alternative polyadenylation, mRNA nuclear export, mRNA stability, circRNA biogenesis, and microRNA maturation, while also performing m6A-independent functions in DNA damage repair and protein stabilization. Its YTH domain recognizes m6A through a Trp377/Trp428 aromatic cage with preferential binding to GG(m6A)C sequences, and structural water networks contribute to selectivity over unmethylated adenosine (PMID:25242552, PMID:26318451, PMID:34258996). YTHDC1 promotes exon inclusion by recruiting SRSF3 while antagonizing SRSF7/SRSF10, facilitates nuclear export of m6A-modified mRNAs and circRNAs through an SRSF3–NXF1 axis, suppresses proximal polyadenylation by sequestering FIP1L1 from CPSF4, and silences retrotransposons by promoting SETDB1-dependent H3K9me3 at LINE1/ERVK loci (PMID:26876937, PMID:28984244, PMID:36094741, PMID:33658714). Its activity is modulated by post-translational modifications—tyrosine phosphorylation by c-Abl/c-Src disperses nuclear condensates and abolishes splicing regulation, O-GlcNAcylation at Ser396 promotes chromatin binding and homologous recombination repair, and lysine lactylation at K82 enhances phase separation to protect oncogenic mRNAs from PAXT-exosome degradation (PMID:15175272, PMID:40242544, PMID:40680722).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1998 Medium

    Initial identification of YTHDC1 as a nuclear splicing-associated factor established that it interacts with Sam68 family members and classical SR splicing factors, placing it at the intersection of RNA binding and pre-mRNA processing.

    Evidence Yeast two-hybrid screen and far Western blotting in rat brain cDNA library

    PMID:9473574

    Open questions at the time
    • Interaction with SC35/SF2 shown only by far Western without reciprocal validation
    • No direct RNA binding or m6A recognition yet known
    • Functional consequence for splicing not demonstrated
  2. 1999 High

    Demonstration that YTHDC1 modulates alternative splice site selection and that its activity is regulated by Src-family kinase phosphorylation of partner Sam68 established YTHDC1 as a functional splicing regulator whose nuclear organization is dynamically controlled.

    Evidence Co-immunoprecipitation, in vivo splicing reporters, p59(fyn) kinase perturbation in mammalian cells

    PMID:10564280

    Open questions at the time
    • RNA substrates not identified transcriptome-wide
    • Direct RNA-binding activity not yet shown
    • Whether YTHDC1 itself is a kinase substrate unknown
  3. 2000 High

    Discovery that YTHDC1 concentrates in novel cell-cycle-regulated nuclear bodies (YT bodies) that depend on active transcription linked its function to transcriptionally active chromatin and defined the domain architecture required for condensate formation.

    Evidence Live-cell imaging, actinomycin D treatment, cell cycle synchronization, deletion analysis

    PMID:10973987

    Open questions at the time
    • Molecular composition of YT bodies unknown
    • Relationship to known nuclear bodies (speckles, paraspeckles) unclear
    • Mechanism of cell-cycle regulation undefined
  4. 2004 High

    Identification of c-Abl and c-Src as direct kinases that phosphorylate YTHDC1, dispersing it from YT bodies and abolishing its splicing activity, established that tyrosine phosphorylation is a major switch controlling YTHDC1 nuclear organization and function.

    Evidence In vivo kinase assays, differential solubility fractionation, splicing reporters for IL-4R/CD44/SRp20

    PMID:15175272

    Open questions at the time
    • Specific tyrosine residues phosphorylated not mapped
    • Physiological signals triggering phosphorylation unknown
    • Whether phosphorylation affects RNA binding directly untested
  5. 2014 High

    The crystal structure of YTHDC1-YTH bound to m6A RNA revealed the aromatic cage mechanism of methyl-group recognition and sequence-context selectivity (GG(m6A)C preference), transforming understanding of YTHDC1 from a generic splicing factor to an m6A-specific reader.

    Evidence X-ray crystallography, biochemical binding assays, PAR-CLIP-seq

    PMID:25242552

    Open questions at the time
    • How m6A reading connects mechanistically to splicing regulation unknown
    • Full-length protein structure unavailable
    • Contribution of disordered regions to function undefined
  6. 2016 High

    The mechanistic basis of YTHDC1-dependent splicing was resolved: m6A-bound YTHDC1 recruits SRSF3 to promote exon inclusion while competitively excluding SRSF7/SRSF10, directly connecting m6A reading to splice-site choice at a transcriptome-wide scale.

    Evidence PAR-CLIP-seq, competitive in vitro pull-down of SRSF3 vs SRSF10, knockdown/rescue with m6A-binding-defective mutant

    PMID:26876937

    Open questions at the time
    • Whether YTHDC1–SRSF3 interaction is direct or RNA-bridged not fully resolved
    • Structural basis of SRSF3/SRSF7 selectivity unknown
    • Contribution to alternative polyadenylation not yet examined
  7. 2017 High

    YTHDC1 was shown to mediate nuclear export of m6A-modified mRNAs through SRSF3 and the NXF1 export receptor, expanding its role beyond splicing to mRNA trafficking and explaining why m6A-marked transcripts accumulate in the nucleus upon YTHDC1 depletion.

    Evidence YTHDC1 knockdown with nuclear/cytoplasmic fractionation, m6A-seq, Co-IP of YTHDC1–SRSF3–NXF1 in HeLa cells

    PMID:28984244

    Open questions at the time
    • Whether export function is separable from splicing function unclear
    • Role of ALYREF and other export adaptors not examined
    • Selectivity for specific m6A transcripts vs bulk effect unknown
  8. 2017 High

    YTHDC1 was found to read METTL16-deposited m6A marks on MAT2A mRNA to trigger its degradation, establishing that YTHDC1 also controls mRNA stability and participates in a SAM-sensing metabolic feedback loop.

    Evidence In vitro METTL16 methylation, YTHDC1 knockdown, MAT2A mRNA stability assays, 3′ UTR m6A site mutagenesis

    PMID:29262316

    Open questions at the time
    • Degradation machinery recruited by YTHDC1 for MAT2A decay not identified
    • Generality of YTHDC1-mediated mRNA decay beyond MAT2A unclear
    • Whether nuclear or cytoplasmic decay pathway is involved unknown
  9. 2018 High

    Conditional knockout in mouse oocytes demonstrated that YTHDC1 is essential for gametogenesis and controls both alternative splicing and alternative polyadenylation in vivo, with m6A-binding ability required for rescue, firmly establishing its physiological necessity.

    Evidence Conditional Ythdc1 KO mouse, RNA-seq (splicing and APA), Co-IP with CPSF6/SRSF3/SRSF7, mutant rescue

    PMID:29799838

    Open questions at the time
    • Relative contribution of splicing vs APA defects to phenotype unresolved
    • Whether YTHDC1 directly interacts with cleavage/polyadenylation machinery not tested biochemically
  10. 2021 High

    Two independent studies demonstrated that YTHDC1 silences retrotransposons (LINE1, ERVK, IAP) in embryonic stem cells by binding their m6A-modified transcripts and promoting SETDB1/KAP1-dependent H3K9me3 deposition, revealing a chromatin-regulatory function that maintains ESC identity and prevents reprogramming to a totipotent-like state.

    Evidence Conditional Ythdc1 KO ESCs, m6A-seq, RIP, H3K9me3 ChIP-seq, genetic epistasis (YTHDC1→SETDB1→H3K9me3), NCL–KAP1 complex analysis

    PMID:33658714 PMID:33886094

    Open questions at the time
    • Mechanism by which m6A-RNA recruits SETDB1 to chromatin not fully delineated
    • Whether RNA acts in cis vs trans at retrotransposon loci unresolved
    • Generality beyond ESC context unknown
  11. 2022 Medium

    YTHDC1 was shown to suppress proximal alternative polyadenylation sites by interacting with FIP1L1 and blocking CPSF4 recruitment, with m6A binding promoting liquid-liquid phase separation of YTHDC1–FIP1L1, providing a mechanistic framework for the APA phenotypes observed in knockout models.

    Evidence APA analysis by RNA-seq, Co-IP of YTHDC1–FIP1L1, in vitro phase separation droplet assays

    PMID:36094741

    Open questions at the time
    • Phase separation reconstitution done in vitro; in vivo relevance of droplets to APA regulation not confirmed
    • Whether FIP1L1 interaction requires m6A or is constitutive not fully resolved
    • Structural basis of YTHDC1–FIP1L1 interaction unknown
  12. 2023 Medium

    An m6A-independent function was uncovered: YTHDC1 promotes TopBP1–MRE11 interaction to activate ATR-mediated DNA damage repair, as demonstrated by rescue with m6A-binding-defective mutants, establishing a dual-function paradigm for YTHDC1.

    Evidence Co-IP (YTHDC1–TopBP1–MRE11), ATR activation assays, in vivo Ythdc1 KO/OE mice, m6A-binding-defective mutant rescue

    PMID:38177310

    Open questions at the time
    • Whether YTHDC1 bridges TopBP1–MRE11 directly or through an RNA scaffold unknown
    • Relative contribution of m6A-dependent vs -independent DDR functions not quantified
    • Single lab finding awaiting independent replication
  13. 2023 Medium

    YTHDC1's post-translational regulation was further expanded: O-GlcNAcylation at Ser396 upon DNA damage promotes chromatin binding, phase separation, m6A-RNA association, and homologous recombination repair, showing that distinct PTMs tune YTHDC1 to different nuclear functions.

    Evidence Ser396 mutagenesis, RIP, FRAP, IRIF imaging, HR reporter assay, molecular dynamics simulations

    PMID:40242544

    Open questions at the time
    • Writer/eraser enzymes for O-GlcNAcylation at this site not fully defined
    • Interplay between O-GlcNAcylation and tyrosine phosphorylation not examined
    • Single lab finding
  14. 2024 High

    A genome-protective pathway was defined in which YTHDC1 cooperates with the THO complex to bind chemically damaged RNA (m1A-containing), preventing R-loop accumulation and XPG-dependent conversion of RNA damage into DNA breaks, revealing that YTHDC1 reads not only m6A but also damage-modified nucleotides.

    Evidence In vitro m1A binding assays, Co-IP (YTHDC1–THOC), R-loop imaging, comet assay, XPG epistasis, RNA dealkylase rescue

    PMID:40037355

    Open questions at the time
    • Whether m1A binding uses the same aromatic cage as m6A not structurally resolved
    • Quantitative contribution of YTHDC1 vs other repair pathways to genome stability unknown
    • Whether damaged RNA clearance is transcriptome-wide or locus-specific undetermined
  15. 2025 High

    Lysine lactylation at K82 by p300 under hypoxia was found to expand YTHDC1 nuclear condensates, protecting oncogenic mRNAs (BCL2, E2F2) from PAXT-exosome-mediated decay, establishing a metabolically responsive PTM–phase separation–mRNA stabilization axis.

    Evidence Lactylome MS, K82 mutagenesis, in vitro droplet assays, nuclear condensate imaging, RIP, PAXT interaction assays, in vivo RCC models

    PMID:40680722

    Open questions at the time
    • Whether lactylation and O-GlcNAcylation cooperate or compete not examined
    • PAXT-exosome substrate selection rules in context of YTHDC1 condensates unknown
    • Generality beyond renal cell carcinoma not established
  16. 2025 Medium

    An m6A-independent protein-stabilization function was revealed: YTHDC1 uses its intrinsically disordered region to bind PPARγ and shield it from ARIH2-mediated ubiquitination and proteasomal degradation, expanding the functional repertoire of YTHDC1 beyond RNA metabolism.

    Evidence Co-IP and domain mapping (YTHDC1–PPARγ–ARIH2), ubiquitination assays, brown adipose tissue-specific Ythdc1 KO, m6A-binding-defective rescue

    PMID:40355558

    Open questions at the time
    • Structural basis of IDR–PPARγ interaction undefined
    • Whether other transcription factors are similarly protected unknown
    • Single lab finding

Open questions

Synthesis pass · forward-looking unresolved questions
  • The full-length structure of YTHDC1 (including disordered regions) and the rules governing how PTMs, phase separation, and RNA/protein partner selection are integrated to allocate YTHDC1 among its many nuclear functions remain unresolved.
  • No full-length YTHDC1 structure available
  • Decision logic for m6A-dependent vs m6A-independent function allocation unknown
  • How phase separation properties are coordinated across multiple PTMs simultaneously is undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 8 GO:0098772 molecular function regulator activity 3 GO:0003677 DNA binding 1
Localization
GO:0005634 nucleus 7 GO:0005654 nucleoplasm 3
Pathway
R-HSA-8953854 Metabolism of RNA 7 R-HSA-73894 DNA Repair 3 R-HSA-4839726 Chromatin organization 2 R-HSA-74160 Gene expression (Transcription) 1 R-HSA-9612973 Autophagy 1
Partners
DDX5ELAVL1EMDFIP1L1KHDRBS1NXF1SRSF3SRSF7
Complex memberships
YTHDC1–FIP1L1 APA regulatory complexYTHDC1–SRSF3–NXF1 export complexYTHDC1–THO complex

Evidence

Reading pass · 47 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 Crystal structure of the YTHDC1 YTH domain in complex with m6A-containing RNA revealed the specific mode of m6A recognition, including an aromatic cage that captures the N6-methyl group and a selective binding pocket that confers preferential recognition of GG(m6A)C sequences. X-ray crystallography, biochemical binding assays, transcriptome-wide PAR-CLIP-seq Nature chemical biology High 25242552
2015 Structural comparison showed that YTHDC1 uniquely harbors a selective binding pocket for the nucleotide preceding m6A (preferring G), distinguishing it from other YTH domain proteins (YTHDF1, YTHDF2, YTHDF3, yeast Pho92), all of which use a conserved aromatic cage but lack the position-specific selectivity of YTHDC1. X-ray crystallography, isothermal titration calorimetry, binding affinity measurements The Journal of biological chemistry High 26318451
1999 YTHDC1 (YT521-B) interacts with the splicing-associated scaffold attachment factor B (SAF-B) and Sam68, localizes to 5–20 large nuclear dots, and modulates alternative splice site selection in a concentration-dependent manner; the Src family kinase p59(fyn)-mediated tyrosine phosphorylation of Sam68 negatively regulates its association with YTHDC1 and dissolves these nuclear dots. Co-immunoprecipitation, in vivo splicing assays, overexpression of p59(fyn), deletion analysis, RNA in situ hybridization Molecular biology of the cell High 10564280
2000 YTHDC1 (YT521-B) localizes to a novel subnuclear structure called YT bodies, which appear at the beginning of S-phase, disperse during mitosis, and are sensitive to actinomycin D (transcription inhibitor), suggesting association with transcriptionally active sites; the glutamic acid-rich N-terminal domain and the C-terminal glutamic acid/arginine-rich domain are required for YT body formation. Live-cell imaging, immunofluorescence, cell cycle synchronization, transcription inhibitor treatment, deletion analysis The Journal of cell biology High 10973987
2003 Emerin (nuclear membrane protein mutated in Emery-Dreifuss muscular dystrophy) directly binds the C-terminal functional domain of YTHDC1 (YT521-B), demonstrated by yeast two-hybrid, pull-down and BIAcore; emerin overexpression inhibits YTHDC1-dependent splice site selection in vivo, defining a bipartite emerin binding site for YTHDC1. Yeast two-hybrid, pull-down assay, BIAcore biomolecular interaction analysis, in vivo splicing assay European journal of biochemistry High 12755701
2004 YTHDC1 (YT521-B) is tyrosine phosphorylated by c-Abl in the nucleus and by c-Src or p59(fyn) in the cytoplasm; tyrosine phosphorylation disperses YTHDC1 from YT bodies to the nucleoplasm into an insoluble form, and abolishes its ability to alter alternative splice site selection of IL-4 receptor, CD44, and SRp20. In vivo kinase assays, differential solubility fractionation, alternative splicing reporter assays, nuclear-cytoplasmic shuttling experiments Human molecular genetics High 15175272
2016 Nuclear m6A reader YTHDC1 promotes exon inclusion in targeted mRNAs by recruiting splicing factor SRSF3 while blocking SRSF7/SRSF10 binding; YTHDC1 facilitates SRSF3 nuclear speckle localization and RNA binding, and represses SRSF10 localization and binding; these effects require the m6A-binding ability of YTHDC1 and were mapped transcriptome-wide by PAR-CLIP-seq. PAR-CLIP-seq, in vitro pull-down (competitive binding of SRSF3 and SRSF10 to YTHDC1), knockdown/rescue with wild-type vs. m6A-binding-defective YTHDC1, nuclear speckle localization assays Molecular cell High 26876937
2017 YTHDC1 mediates nuclear export of m6A-methylated mRNAs in HeLa cells; knockdown of YTHDC1 causes nuclear accumulation and cytoplasmic depletion of m6A-containing transcripts; mechanistically, YTHDC1 interacts with splicing factor/nuclear export adaptor SRSF3 and facilitates RNA binding to both SRSF3 and the export receptor NXF1. YTHDC1 knockdown, nuclear/cytoplasmic fractionation, m6A-seq, Co-IP (YTHDC1–SRSF3–NXF1) eLife High 28984244
2017 YTHDC1 reads METTL16-deposited m6A marks in the 3′ UTR of MAT2A mRNA to promote its degradation; when SAM is depleted, METTL16 methylation of MAT2A is reduced, YTHDC1-dependent decay is relieved, and MAT2A mRNA is stabilized, thus upregulating SAM synthesis as a feedback mechanism. In vitro methylation assays with recombinant METTL16, YTHDC1 knockdown, MAT2A mRNA stability assays, 3′ UTR mutagenesis of m6A target adenines Cell reports High 29262316
2018 YTHDC1 is essential for spermatogonial development and oocyte growth/maturation in mice; loss of YTHDC1 in oocytes causes extensive alternative polyadenylation (altered 3′ UTR length) and massive alternative splicing defects; splicing defects are rescued by wild-type but not m6A-binding-deficient YTHDC1; YTHDC1 associates with pre-mRNA 3′ end processing factors CPSF6, SRSF3, and SRSF7. Conditional knockout mouse, RNA-seq, alternative splicing analysis, polyadenylation analysis, Co-IP (YTHDC1–CPSF6/SRSF3/SRSF7), rescue with separation-of-function mutant PLoS genetics High 29799838
2019 Atomistic simulations and X-ray crystallography show that the m6A methyl group is captured by the aromatic cage of YTHDC1 (Trp377/Trp428), the 3′ terminus nucleotides are stabilized by cation-π-π interactions, and the 5′ terminus remains flexible; the methyl group of m6A pre-organizes the RNA into a bound-like conformation, facilitating association. X-ray crystallography, atomistic molecular dynamics simulations, isothermal titration calorimetry Journal of chemical theory and computation High 31670957
2019 Oncogene metadherin (MTDH) interacts with YTHDC1, Sam68, and T-STAR in nuclear speckles and influences alternative splice site selection of CD44 in a dose-dependent manner. Yeast two-hybrid, co-immunoprecipitation, CD44v5-luc minigene splicing reporter assay Cancers Medium 31450747
2020 The YTH domain of YTHDC1 binds N6-methyladenine in single-stranded DNA with ~10 nM Kd, approximately 5-fold stronger than the equivalent m6A RNA under the same conditions; crystal structures of YTHDC1 YTH in complex with N6mA-containing ssDNA showed recognition of methylated adenine in a single-stranded region flanked by duplexed DNA. Fluorescence polarization binding assay, X-ray crystallography (two structures) Nucleic acids research High 32663306
2021 YTHDC1 is required for maintenance of mouse embryonic stem cells; deletion triggers reprogramming to a 2C-like state; mechanistically, YTHDC1 binds m6A-modified retrotransposon (IAP, ERVK, LINE1) transcripts and its depletion results in reactivation of these elements accompanied by global decrease in SETDB1-mediated H3K9me3; YTHDC1 and its target m6A RNAs act upstream of SETDB1 to repress retrotransposons and Dux. Conditional knockout ESCs, RNA-seq, m6A-seq, YTHDC1 RIP, H3K9me3 ChIP-seq, genetic epistasis (YTHDC1 → SETDB1 → H3K9me3) Nature High 33658714
2021 YTHDC1 recognizes m6A on LINE1 RNAs in the nucleus, regulates the formation of the LINE1–nucleolin (NCL) RNA scaffold partnership, promotes chromatin recruitment of KAP1, and is required for H3K9me3 establishment on 2C-related retrotransposons; YTHDC1 is also required for sufficient rRNA synthesis in ESCs. Conditional Ythdc1 KO in ESCs, RIP, Co-IP (LINE1 RNA–NCL–KAP1 complex), H3K9me3 ChIP-seq, rRNA synthesis assay Protein & cell High 33886094
2021 YTHDC1 regulates leukemogenesis through MCM4, a critical regulator of DNA replication; genetic deletion of Ythdc1 blocks AML development and LSC self-renewal in vivo; haploinsufficiency reduces LSC but not normal HSC self-renewal. Conditional Ythdc1 KO mouse models, in vivo AML transplantation, YTHDC1 knockdown in primary AML cells, MCM4 target identification Blood High 34255814
2021 Trp428 of YTHDC1 switches between two conformational states to build and dismantle the aromatic cage for m6A binding; Met438 and Ser378 modulate binding enthalpy-entropy compensation without changing affinity; Thr379Val mutation significantly reduces thermal stability and m6A binding capability; a structural water molecule synergistically binds YTHDC1 with m6A as a hydrogen-bond hub. Atomistic MD simulations, site-directed mutagenesis, thermal shift assay, isothermal titration calorimetry, free energy calculations Journal of chemical theory and computation High 33472367
2021 YTHDC1 interacts with ELAVL1/HuR to modulate SQSTM1 mRNA stability in the nucleus; YTHDC1 knockdown causes SQSTM1 mRNA degradation in the nucleus, blocking autophagic flux; overexpression of YTHDC1 rescues the autophagic flux blockade induced by high glucose in keratinocytes. Co-IP (YTHDC1–ELAVL1), RIP-qPCR (YTHDC1 binding to SQSTM1 mRNA), YTHDC1 KD/OE, autophagic flux assays (LC3, autophagosome imaging), in vivo Ythdc1/Sqstm1 knockdown Autophagy Medium 34657574
2021 Molecular dynamics and NMR analysis of the YTHDC1 YTH–m6A RNA complex revealed that structured water molecules surrounding the bound RNA contribute to m6A selectivity; bulk water intrusions disrupt unmethylated adenosine binding; the 5′-G preference of YTHDC1 is partially mediated by a water-mediated hydrogen bond network between the guanosine 2-amino group and binding pocket residues; D479A mutation disrupts this water network. MD simulations, NMR spectroscopy, isothermal titration calorimetry The journal of physical chemistry. B High 34258996
2021 YTHDC1 facilitates biogenesis of mature miR-30d via m6A-mediated regulation of mRNA stability; mature miR-30d then inhibits aerobic glycolysis by reducing SLC2A1 and HK1 expression through targeting transcription factor RUNX1. MeRIP, RIP, RNA stability assay, miRNA maturation analysis, luciferase reporter assay Cell death and differentiation Medium 34021267
2022 NMR solution structure of the m6A-modified AUCG tetraloop hairpin of Xist A-repeats showed that m6A extends 5′ stacking of the helical stem; crystal structure of YTHDC1 bound to the (m6A)UCG tetraloop showed recognition in single-stranded conformation requiring local unfolding of the upper stem; fluorescence quenching confirmed that binding requires local stem unfolding. NMR structure determination, X-ray crystallography, fluorescence quenching experiments Nucleic acids research High 35166835
2022 Nuclear AURKA disrupts binding of SRSF3 to YTHDC1 (blocking m6A-YTHDC1-SRSF3-dependent RBM4-FL production) and instead recruits hnRNP K to YTHDC1, creating an m6A-YTHDC1-hnRNP K complex that promotes exon skipping to produce the oncogenic RBM4-S isoform; AURKA nuclear translocation is required but its kinase activity is not. Co-IP (AURKA–YTHDC1–SRSF3/hnRNP K complexes), alternative splicing analysis, nuclear translocation blocking experiments, kinase-dead mutants Signal transduction and targeted therapy Medium 35361747
2022 SRSF3 binding to YTHDC1 is regulated by the phosphorylation status of SRSF3's arginine/serine-rich (RS) domain; dephosphorylation-mimic serine-to-alanine mutants of SRSF3 revealed multiple phosphorylation positions; YTHDC1 binding involves both YTHDC1 N- and C-terminal residues as well as the RS domain and additional regions of SRSF3. Co-immunoprecipitation with deletion mutants, dephosphorylation-mimic mutagenesis (S→A), domain mapping Cells Medium 35563766
2022 YTHDC1 suppresses proximal alternative polyadenylation (APA) sites to produce longer 3′ UTR transcripts; mechanistically, YTHDC1 directly interacts with 3′ end processing factor FIP1L1 and interferes with its ability to recruit CPSF4; m6A binding promotes liquid-liquid phase separation of YTHDC1 and FIP1L1. APA analysis (RNA-seq), Co-IP (YTHDC1–FIP1L1), RIP, phase separation assays (in vitro droplet formation), YTHDC1 KD EMBO reports Medium 36094741
2022 YTHDC1 promotes nuclear export of SMAD3 mRNA in an m6A-dependent manner; YTHDC1 depletion causes nuclear retention of SMAD3 mRNA and lower SMAD3 protein levels, impairing TGF-β-induced EMT and TNBC cell migration; m6A-binding-defective YTHDC1 cannot rescue these phenotypes. YTHDC1 KO/rescue with m6A-binding mutant, nuclear/cytoplasmic fractionation, RIP-seq, m6A-seq, cell migration/invasion assays, in vivo metastasis model Theranostics Medium 35966596
2022 YTHDC1 binding to m6A sites on HIV-1 transcripts (in a METTL3-dependent manner) regulates viral RNA biogenesis: YTHDC1 knockdown increases unspliced and incompletely spliced HIV-1 RNAs, reduces Env and Vpu protein expression, leads to incorporation of unprocessed gp160 into virions, and reduces virion infectivity. YTHDC1 knockdown, HIV-1 RNA splicing analysis, viral protein Western blot, RIP (YTHDC1 binding to HIV-1 transcripts), viral infectivity assay Retrovirology Medium 35101069
2023 YTHDC1 is an essential regulator of satellite cell (muscle stem cell) activation and proliferation; YTHDC1 depletion nearly abolishes regenerative capacity; YTHDC1 regulates mRNA splicing and nuclear export of target transcripts; hnRNPG is identified as a bona fide YTHDC1 interacting partner in myoblasts. Inducible Ythdc1 KO in satellite cells, LACE-seq (transcriptome-wide binding), splicing analysis, nuclear export analysis, Co-IP interactome mapping eLife High 36892464
2023 YTHDC1 binding to m6A sites in the FSP1 3′-UTR recruits alternative polyadenylation regulator CSTF3 to generate a less stable shorter 3′-UTR FSP1 mRNA; YTHDC1 downregulation generates longer 3′-UTR FSP1 mRNA stabilized by HuR, leading to elevated FSP1 protein and ferroptosis resistance in lung cancer. RIP (YTHDC1–FSP1 mRNA), APA analysis, Co-IP (YTHDC1–CSTF3), RNA stability assays, HuR interaction assays, YTHDC1 KD rescue experiments Cell death and differentiation Medium 37903990
2023 YTHDC1 and the RNA helicase DDX5 interact directly and cooperate to promote the production of a common subset of circRNAs in rhabdomyosarcoma cells through the back-splicing reaction; DDX5 acts as a co-factor of the m6A regulatory network downstream of YTHDC1. Co-IP (YTHDC1–DDX5), circRNA-seq, YTHDC1/DDX5 depletion, back-splicing assays Nature communications Medium 37019933
2023 YTHDC1 regulates muscle stem cell quiescence exit via PI4K-Akt-mTOR signaling; Ythdc1-null satellite cells cannot exit quiescence; mechanistically, YTHDC1 binds m6A-modified Pi4k2a and Pi4kb mRNAs to regulate their alternative splicing, sustaining PI4K-Akt-mTOR pathway activity. Conditional Ythdc1 KO in satellite cells, phospho-signaling assays (p-Akt, p-S6), splicing analysis of Pi4k2a/Pi4kb, RIP Cell proliferation Medium 36722312
2023 YTHDC1 delays stress-induced pulmonary senescence and fibrosis through an m6A-independent mechanism: it promotes interaction between TopBP1 and MRE11, thereby activating ATR and facilitating DNA damage repair; this function is independent of m6A-binding ability. Co-IP (YTHDC1–TopBP1–MRE11), ATR activation assays, YTHDC1 KO/OE in mice, rescue with m6A-binding-defective YTHDC1 mutant The EMBO journal Medium 38177310
2023 YTHDC1 inhibits influenza A virus NS segment splicing by binding to the NS 3′ splicing site in an m6A-dependent manner, thereby promoting viral replication and pathogenicity; YTHDC1 levels are enhanced by IAV infection, and its depletion reduces viral replication. YTHDC1 KD/OE, NS mRNA splicing analysis, RIP (YTHDC1–NS RNA), in vivo IAV infection model PLoS pathogens Medium 37053288
2023 YTHDC1 promotes the nuclear export of m6A-modified circRNAs (e.g., circKcnk9) in an m6A-dependent manner; siYTHDC1 increases nuclear staining of circKcnk9, which is reversed by wild-type but not m6A-binding-defective YTHDC1. RNA FISH, siRNA KD, YTHDC1 wild-type vs. mutant rescue, YTHDC1 RIP on circKcnk9 Molecular pain Medium 36443649
2023 YTHDC1 regulates the splicing of HOXB-AS3 precursor RNA via m6A modification, upregulating the NR_033205.1 spliceosome isoform, which accelerates leukemic stem cell self-renewal and AML progression. m6A-MeRIP, RIP (YTHDC1 binding to HOXB-AS3), splicing analysis, KD/OE functional assays in THP-1 and mouse models International journal of biological macromolecules Medium 36906205
2023 YTHDC1 binds to the transcription start sites of TP53 and other DNA damage response genes, promoting their transcriptional elongation in an m6A-independent manner; YTHDC1 also reduces intron retention in m6A-dependent fashion for key DDR factors; YTHDC1 deficiency causes genomic instability. CRISPR-KO screen, YTHDC1 ChIP (TSS binding), RNA-seq (intron retention analysis), m6A-dependent vs -independent rescue experiments The EMBO journal Medium 38951610
2023 Depletion of YTHDC1 in cardiomyocytes causes dilated cardiomyopathy; YTHDC1 binds m6A-modified Titin mRNA and its depletion results in aberrant splicing of Titin, leading to disordered sarcomere arrangement and decreased cardiomyocyte contractility. Cardiac-specific conditional Ythdc1 KO, m6A-MeRIP-seq, RIP-seq, mRNA-seq, sarcomere imaging Journal of cellular and molecular medicine Medium 34716659
2023 YTHDC1 O-GlcNAcylation at Ser396 (mediated upon DNA damage) promotes YTHDC1 chromatin binding, IRIF formation, m6A RNA binding, and liquid-liquid phase separation of YTHDC1 condensates at damage sites; O-GlcNAcylated YTHDC1 promotes homologous recombination-mediated repair and recruitment of Rad51. Site-directed mutagenesis (Ser396), RIP (m6A binding), Co-IP, FRAP, IRIF immunofluorescence, HR reporter assay, molecular dynamics simulations Fundamental research Medium 40242544
2024 YTHDC1 interacts with the THO complex (THOC) and, in addition to binding m6A, binds chemically damaged N1-methyladenosine (m1A) in RNA; without YTHDC1 or THOC, damaged nuclear RNA accumulates R-loops that are converted to DNA breaks (RDIBs) by the XPG nuclease; an RNA-specific dealkylase rescues the DNA break phenotype, establishing that RNA damage drives genome instability. In vitro binding assays (m1A vs m6A), Co-IP (YTHDC1–THOC), R-loop immunofluorescence, comet assay, XPG epistasis, RNA dealkylase rescue Molecular cell High 40037355
2024 DDX41 promotes YTHDC1 recruitment to m6A-methylated R-loops by facilitating the interaction between METTL3 and YTHDC1; DDX41 loss (KO or patient mutations R525H/Y259C) impairs this interaction, leading to increased m6A-RNA methylated R-loops and genomic instability. DDX41 KO and knock-in cell lines, Co-IP (DDX41–METTL3–YTHDC1 complex), m6A quantification, R-loop immunofluorescence, primary MDS patient samples Leukemia Medium 38514771
2024 YTHDC1 binds m6A-modified KMT2C mRNA to stabilize it; KMT2C catalyzes H3K4 methylation required for expression of DNA damage response genes; YTHDC1 knockdown decreases YTHDC1 protein stability, reduces KMT2C levels, and attenuates DDR gene expression, sensitizing B-ALL cells to chemotherapy. RIP-qPCR (YTHDC1–KMT2C mRNA), RNA stability assay, H3K4 ChIP, YTHDC1/KMT2C KD, B-ALL xenograft model, molecular docking for inhibitor identification Leukemia Medium 39501105
2024 YTHDC1 interacts with HP1BP3 (a nuclear RNA binding protein involved in microRNA maturation); YTHDC1 deficiency in HSCs causes significant alterations in microRNA levels (including mir-125b, mir-99b, let-7e); overexpression of these miRNAs partially rescues YTHDC1-null HSC functional defects, establishing a YTHDC1–HP1BP3–microRNA maturation axis for HSC maintenance. Conditional Ythdc1 KO, Ythdc1/Mettl3 double KO, Co-IP (YTHDC1–HP1BP3), small RNA-seq, miRNA rescue experiments Cell death discovery Medium 39414764
2024 KAP1 (TRIM28) forms a complex with YTHDC1 and METTL3 to stabilize m6A-modified MYCN mRNA; KAP1 depletion decreases YTHDC1 protein stability and promotes MYCN mRNA degradation; MYCN in turn transcriptionally activates KAP1, forming a positive feedback loop. Co-IP/mass spectrometry (KAP1–YTHDC1–METTL3 complex), RIP-qPCR, RNA stability assay, Western blot, xenograft model Journal of experimental & clinical cancer research Medium 38745192
2025 Lysine lactylation of YTHDC1 at K82 (mediated by p300 under hypoxia) increases YTHDC1 phase separation and expansion of nuclear condensates, protecting oncogenic BCL2 and E2F2 mRNAs from degradation by the PAXT-exosome complex in renal cell carcinoma cells. Lactylome mass spectrometry, K82 mutagenesis, phase separation assays (in vitro droplets, nuclear condensate imaging), RIP (YTHDC1–BCL2/E2F2 mRNA), PAXT-exosome interaction assays, in vivo RCC models Molecular cell High 40680722
2025 YTHDC1 directly interacts with PPARγ through its intrinsically disordered region (IDR), protecting PPARγ from ARIH2 E3 ubiquitin ligase-mediated ubiquitination and proteasomal degradation; the ARIH2 RING2 domain is essential for PPARγ degradation, and the PPARγ A/B domain mediates the interaction with ARIH2; this function is independent of YTHDC1's m6A-binding ability. Co-IP (YTHDC1–PPARγ–ARIH2), domain mapping, ubiquitination assays, Ythdc1 KO in brown adipose tissue, m6A-binding-defective YTHDC1 rescue The EMBO journal Medium 40355558
2025 Phase-separating YTHDC1 forms a nuclear pore complex with SRSF3, ALYREF, and exportin-5 (XPO5) to promote nuclear export of m6A-modified lncRNA lnc668; this process requires YTHDC1 phase separation and is dependent on METTL3-mediated m6A modification of lnc668. Co-IP (YTHDC1–SRSF3–ALYREF–XPO5), phase separation assays, FISH (nuclear/cytoplasmic lnc668), MeRIP, YTHDC1 KD in fibrosis models Cell death & disease Medium 40221424
2024 Structure-based medicinal chemistry yielded YTHDC1 inhibitor compound 40 (Kd = 49 nM), validated by a 1.6 Å crystal structure of the complex; compound 40 is selective over cytoplasmic YTHDF1-3 and YTHDC2, shows antiproliferative activity against AML cell lines, and engages YTHDC1 in cells (confirmed by CETSA). X-ray crystallography (1.6 Å), biochemical binding assay, selectivity panel, antiproliferative assay, cellular thermal shift assay (CETSA) Journal of medicinal chemistry High 38787793
1998 YTHDC1 (YT521) was identified as an RA301 (Sam68 paralog) binding protein by yeast two-hybrid screening; far Western blot showed that YT521 protein interacts with RA301, and also with splicing factors SC35 and SF2, suggesting a role as an RNA splicing-related protein; YT521 mRNA is induced by hypoxia/reoxygenation through reactive oxygen species. Yeast two-hybrid screening, far Western blot (YT521–RA301, SC35, SF2 interactions) Brain research. Molecular brain research Medium 9473574

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 Nuclear m(6)A Reader YTHDC1 Regulates mRNA Splicing. Molecular cell 1673 26876937
2017 YTHDC1 mediates nuclear export of N6-methyladenosine methylated mRNAs. eLife 1037 28984244
2014 Structural basis for selective binding of m6A RNA by the YTHDC1 YTH domain. Nature chemical biology 592 25242552
2018 Nuclear m6A reader YTHDC1 regulates alternative polyadenylation and splicing during mouse oocyte development. PLoS genetics 452 29799838
2021 The RNA m6A reader YTHDC1 silences retrotransposons and guards ES cell identity. Nature 293 33658714
2017 S-Adenosylmethionine Synthesis Is Regulated by Selective N6-Adenosine Methylation and mRNA Degradation Involving METTL16 and YTHDC1. Cell reports 293 29262316
2015 Structural Basis for the Discriminative Recognition of N6-Methyladenosine RNA by the Human YT521-B Homology Domain Family of Proteins. The Journal of biological chemistry 273 26318451
1999 The interaction and colocalization of Sam68 with the splicing-associated factor YT521-B in nuclear dots is regulated by the Src family kinase p59(fyn). Molecular biology of the cell 167 10564280
2020 N6 -Methyladenosine Reader Protein YT521-B Homology Domain-Containing 2 Suppresses Liver Steatosis by Regulation of mRNA Stability of Lipogenic Genes. Hepatology (Baltimore, Md.) 161 32150756
2021 YTHDC1-mediated augmentation of miR-30d in repressing pancreatic tumorigenesis via attenuation of RUNX1-induced transcriptional activation of Warburg effect. Cell death and differentiation 147 34021267
2021 m6A reader YTHDC1 modulates autophagy by targeting SQSTM1 in diabetic skin. Autophagy 145 34657574
2021 Nuclear m6A reader YTHDC1 regulates the scaffold function of LINE1 RNA in mouse ESCs and early embryos. Protein & cell 137 33886094
2021 A critical role of nuclear m6A reader YTHDC1 in leukemogenesis by regulating MCM complex-mediated DNA replication. Blood 128 34255814
2016 Nuclear m(6)A Reader YTHDC1 Regulates mRNA Splicing. Trends in genetics : TIG 123 27050931
2021 The multifaceted effects of YTHDC1-mediated nuclear m6A recognition. Trends in genetics : TIG 97 34920906
2000 The ER repeat protein YT521-B localizes to a novel subnuclear compartment. The Journal of cell biology 90 10973987
2003 Emerin interacts in vitro with the splicing-associated factor, YT521-B. European journal of biochemistry 84 12755701
2023 YTHDC1 as a tumor progression suppressor through modulating FSP1-dependent ferroptosis suppression in lung cancer. Cell death and differentiation 73 37903990
2023 Nuclear m6A reader YTHDC1 promotes muscle stem cell activation/proliferation by regulating mRNA splicing and nuclear export. eLife 63 36892464
2022 Nuclear Aurora kinase A switches m6A reader YTHDC1 to enhance an oncogenic RNA splicing of tumor suppressor RBM4. Signal transduction and targeted therapy 60 35361747
2022 YTHDC1 is downregulated by the YY1/HDAC2 complex and controls the sensitivity of ccRCC to sunitinib by targeting the ANXA1-MAPK pathway. Journal of experimental & clinical cancer research : CR 59 35974388
1998 Cloning of a gene, YT521, for a novel RNA splicing-related protein induced by hypoxia/reoxygenation. Brain research. Molecular brain research 57 9473574
2022 RNA N -methyladenosine reader YTHDC1 is essential for TGF-beta-mediated metastasis of triple negative breast cancer. Theranostics 52 35966596
2021 The RNA Binding Proteins YTHDC1 and FMRP Regulate the Nuclear Export of N6-Methyladenosine-Modified Hepatitis B Virus Transcripts and Affect the Viral Life Cycle. Journal of virology 52 33883220
2004 The intranuclear localization and function of YT521-B is regulated by tyrosine phosphorylation. Human molecular genetics 49 15175272
2023 YTHDC1 positively regulates PTEN expression and plays a critical role in cisplatin resistance of bladder cancer. Cell proliferation 44 37070134
2022 Structural effects of m6A modification of the Xist A-repeat AUCG tetraloop and its recognition by YTHDC1. Nucleic acids research 44 35166835
2024 NAT10 mediated ac4C acetylation driven m6A modification via involvement of YTHDC1-LDHA/PFKM regulates glycolysis and promotes osteosarcoma. Cell communication and signaling : CCS 42 38233839
2023 The m6A reader YTHDC1 and the RNA helicase DDX5 control the production of rhabdomyosarcoma-enriched circRNAs. Nature communications 42 37019933
2019 The Oncogene Metadherin Interacts with the Known Splicing Proteins YTHDC1, Sam68 and T-STAR and Plays a Novel Role in Alternative mRNA Splicing. Cancers 40 31450747
2023 YTHDC1 delays cellular senescence and pulmonary fibrosis by activating ATR in an m6A-independent manner. The EMBO journal 37 38177310
2020 Biochemical and structural basis for YTH domain of human YTHDC1 binding to methylated adenine in DNA. Nucleic acids research 37 32663306
2019 N6-Methyladenosine detected in RNA of testicular germ cell tumors is controlled by METTL3, ALKBH5, YTHDC1/F1/F2, and HNRNPC as writers, erasers, and readers. Andrology 36 30903744
2021 YTHDC1-mediated VPS25 regulates cell cycle by targeting JAK-STAT signaling in human glioma cells. Cancer cell international 32 34863175
2021 Depletion of m6 A reader protein YTHDC1 induces dilated cardiomyopathy by abnormal splicing of Titin. Journal of cellular and molecular medicine 30 34716659
2023 The YTHDC1/GLUT3/RNF183 axis forms a positive feedback loop that modulates glucose metabolism and bladder cancer progression. Experimental & molecular medicine 29 37258572
2023 WTAP activates MAPK signaling through m6A methylation in VEGFA mRNA-mediated by YTHDC1 to promote colorectal cancer development. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 29 37428639
2024 Impaired binding affinity of YTHDC1 with METTL3/METTL14 results in R-loop accumulation in myelodysplastic neoplasms with DDX41 mutation. Leukemia 28 38514771
2023 A potassium-chloride co-transporter promotes tumor progression and castration resistance of prostate cancer through m6A reader YTHDC1. Cell death & disease 28 36609444
2023 The Loss of YTHDC1 in Gut Macrophages Exacerbates Inflammatory Bowel Disease. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 28 36922750
2022 MiR-451a promotes cell growth, migration and EMT in osteosarcoma by regulating YTHDC1-mediated m6A methylation to activate the AKT/mTOR signaling pathway. Journal of bone oncology 27 35198364
2022 Downregulation of the m6A reader protein YTHDC1 leads to islet β-cell failure and diabetes. Metabolism: clinical and experimental 27 36302453
2022 Nuclear m6 A reader YTHDC1 suppresses proximal alternative polyadenylation sites by interfering with the 3' processing machinery. EMBO reports 25 36094741
2024 KIAA1429 facilitates metastasis via m6A-YTHDC1-dependent RND3 down-regulation in hepatocellular carcinoma cells. Cancer letters 24 38224863
2024 Histone lactylation-driven YTHDC1 promotes hepatocellular carcinoma progression via lipid metabolism remodeling. Cancer letters 24 39725144
2023 The m6A reader YTHDC1 regulates muscle stem cell proliferation via PI4K-Akt-mTOR signalling. Cell proliferation 23 36722312
2021 LINC00857 promotes cell proliferation and migration in colorectal cancer by interacting with YTHDC1 and stabilizing SLC7A5. Oncology letters 23 34122629
2023 N6-methyladenosine reader protein YTHDC1 regulates influenza A virus NS segment splicing and replication. PLoS pathogens 22 37053288
2022 YTHDC1 regulates distinct post-integration steps of HIV-1 replication and is important for viral infectivity. Retrovirology 21 35101069
2019 Flexible Binding of m6A Reader Protein YTHDC1 to Its Preferred RNA Motif. Journal of chemical theory and computation 21 31670957
2023 METTL3/YTHDC1-medicated m6A modification of circRNA3634 regulates the proliferation and differentiation of antler chondrocytes by miR-124486-5-MAPK1 axis. Cellular & molecular biology letters 20 38062349
2021 Atomistic and Thermodynamic Analysis of N6-Methyladenosine (m6A) Recognition by the Reader Domain of YTHDC1. Journal of chemical theory and computation 20 33472367
2025 YTHDC1 lactylation regulates its phase separation to enhance target mRNA stability and promote RCC progression. Molecular cell 19 40680722
2024 Structure-Based Design of a Potent and Selective YTHDC1 Ligand. Journal of medicinal chemistry 19 38787793
2025 High-glucose-associated YTHDC1 lactylation reduces the sensitivity of bladder cancer to enfortumab vedotin therapy. Cell reports 18 40215164
2023 Low expression of m6A reader YTHDC1 promotes progression of ovarian cancer via PIK3R1/STAT3/GANAB axis. International journal of biological sciences 18 37781028
2020 YTHDC1 gene polymorphisms and hepatoblastoma susceptibility in Chinese children: A seven-center case-control study. The journal of gene medicine 17 32729171
2023 Alternative splicing of HOXB-AS3 underlie the promoting effect of nuclear m6A reader YTHDC1 on the self-renewal of leukemic stem cells in acute myeloid leukemia. International journal of biological macromolecules 16 36906205
2023 METTL3/YTHDC1-mediated upregulation of LINC00294 promotes hepatocellular carcinoma progression. Heliyon 16 38125436
2021 Recognition of N6-Methyladenosine by the YTHDC1 YTH Domain Studied by Molecular Dynamics and NMR Spectroscopy: The Role of Hydration. The journal of physical chemistry. B 15 34258996
2024 YTHDC1 is a therapeutic target for B-cell acute lymphoblastic leukemia by attenuating DNA damage response through the KMT2C-H3K4me1/me3 epigenetic axis. Leukemia 14 39501105
2023 YTHDC1 maintains trophoblasts function by promoting degradation of m6A-modified circMPP1. Biochemical pharmacology 14 36780989
2025 YTHDC1 phase separation drives the nuclear export of m6A-modified lncNONMMUT062668.2 through the transport complex SRSF3-ALYREF-XPO5 to aggravate pulmonary fibrosis. Cell death & disease 13 40221424
2024 YTHDC1-dependent m6A modification modulated FOXM1 promotes glycolysis and tumor progression through CENPA in triple-negative breast cancer. Cancer science 13 38566554
2024 YTHDC1 aggravates high glucose-induced retinal vascular endothelial cell injury via m6A modification of CDK6. Biology direct 13 38978074
2023 The Effect of N6-Methyladenosine Regulators and m6A Reader YTHDC1-Mediated N6-Methyladenosine Modification Is Involved in Oxidative Stress in Human Aortic Dissection. Oxidative medicine and cellular longevity 13 36819785
2023 SILENCING M 6 A READER YTHDC1 REDUCES INFLAMMATORY RESPONSE IN SEPSIS-INDUCED CARDIOMYOPATHY BY INHIBITING SERPINA3N EXPRESSION. Shock (Augusta, Ga.) 13 36877222
2021 YTHDC1 gene polymorphisms and neuroblastoma susceptibility in Chinese children. Aging 13 34897032
2025 YTHDC1 cooperates with the THO complex to prevent RNA-damage-induced DNA breaks. Molecular cell 12 40037355
2023 Reduction of mRNA m6A associates with glucose metabolism via YTHDC1 in human and mice. Diabetes research and clinical practice 12 36878322
2022 Overexpression of m6A-factors METTL3, ALKBH5, and YTHDC1 alters HPV16 mRNA splicing. Virus genes 11 35190939
2022 YTHDC1 Promotes Stemness Maintenance and Malignant Progression in Head and Neck Squamous Cell Carcinoma. Stem cells international 11 36411870
2015 YT521 promotes metastases of endometrial cancer by differential splicing of vascular endothelial growth factor A. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 11 26289848
2013 The evaluation of the FOXO1, KLF9 and YT521 genes expression in human endometrial cancer. Clinical laboratory 11 23865345
2024 The METTL3-m6A-YTHDC1-AMIGO2 axis contributes to cell proliferation and migration in esophageal squamous cell carcinoma. Gene 10 38360124
2024 KAP1 stabilizes MYCN mRNA and promotes neuroblastoma tumorigenicity by protecting the RNA m6A reader YTHDC1 protein degradation. Journal of experimental & clinical cancer research : CR 10 38745192
2024 YTHDC1 m6A-dependent and m6A-independent functions converge to preserve the DNA damage response. The EMBO journal 10 38951610
2024 METTL3 mediates m6A modification of lncRNA CRNDE to promote ATG10 expression and improve brain ischemia/reperfusion injury through YTHDC1. Biology direct 10 39407279
2025 piR-26441 inhibits mitochondrial oxidative phosphorylation and tumorigenesis in ovarian cancer through m6A modification by interacting with YTHDC1. Cell death & disease 9 39827178
2024 YTHDC1 inhibits osteoclast differentiation to alleviate osteoporosis by enhancing PTPN6 messenger RNA stability in an m6A-hUR-dependent manner. Journal of leukocyte biology 9 38289832
2024 Mir22hg facilitates ferritinophagy-mediated ferroptosis in sepsis by recruiting the m6A reader YTHDC1 and enhancing Angptl4 mRNA stability. Journal of bioenergetics and biomembranes 9 38842666
2023 YT521-B homology domain containing 1 ameliorates mitochondrial damage and ferroptosis in sleep deprivation by activating the sirtuin 1/nuclear factor erythroid-derived 2-like 2/heme oxygenase 1 pathway. Brain research bulletin 9 36935054
2023 YTHDC1-Modified m6A Methylation of Hsa_circ_0102678 Promotes Keratinocyte Inflammation Induced by Cutibacterium acnes Biofilm through Regulating miR-146a/TRAF6 and IRAK1 Axis. Journal of innate immunity 9 37903473
2022 Methyltransferase-like 3 modulates visceral hypersensitivity through regulating the nuclear export of circKcnk9 in YTHDC1-dependent manner. Molecular pain 9 36443649
2025 The YTHDC1 reader protein recognizes and regulates the lncRNA MEG3 following its METTL3-mediated m6A methylation: a novel mechanism early during radiation-induced liver injury. Cell death & disease 8 39994235
2025 YTHDC1 promotes postnatal brown adipose tissue development and thermogenesis by stabilizing PPARγ. The EMBO journal 8 40355558
2024 Fat Mass and Obesity-Associated Protein Regulates Granulosa Cell Aging by Targeting Matrix Metalloproteinase-2 Gene Via an N6-Methyladenosine-YT521-B Homology Domain Family Member 2-Dependent Pathway in Aged Mice. Reproductive sciences (Thousand Oaks, Calif.) 8 38995602
2024 YTHDC1-mediated microRNA maturation is essential for hematopoietic stem cells maintenance. Cell death discovery 8 39414764
2025 ALKBH5 facilitates tumor progression via an m6A-YTHDC1-dependent mechanism in glioma. Cancer letters 7 39761866
2024 Endothelial downregulation of nuclear m6A reader YTHDC1 promotes pulmonary vascular remodeling in sugen hypoxia model of pulmonary hypertension. Heliyon 7 38318069
2024 METTL14/YTHDC1-Mediated m6A Modification in Hippocampus Improves Pentylenetetrazol-Induced Acute Seizures. Molecular neurobiology 7 38814536
2024 YTHDC1 inhibits autophagy-dependent NF-κB signaling by stabilizing Beclin1 mRNA in macrophages. Journal of inflammation (London, England) 7 38877444
2024 N6-methyladenosine demethylase FTO regulates neuronal oxidative stress via YTHDC1-ATF3 axis in arsenic-induced cognitive dysfunction. Journal of hazardous materials 7 39265400
2024 YTHDC1 Regulates the Migration, Invasion, Proliferation, and Apoptosis of Rheumatoid Fibroblast-Like Synoviocytes. Frontiers in immunology 7 39534605
2023 The m6A reader YTHDC1-mediated lncRNA CTBP1-AS2 m6A modification accelerates cholangiocarcinoma progression. Heliyon 7 37809459
2023 DNA damage-induced YTHDC1 O-GlcNAcylation promotes homologous recombination by enhancing m6A binding. Fundamental research 7 40242544
2021 YTHDC1 gene polymorphisms and Wilms tumor susceptibility in Chinese children: A five-center case-control study. Gene 7 33737126
2024 m6A Reader YTHDC1 Impairs Respiratory Syncytial Virus Infection by Downregulating Membrane CX3CR1 Expression. Viruses 6 38793659
2024 Functional role of lncRNA MEG3 on pyroptosis through interacting with EZH2 and YTHDC1 in postoperative cognitive dysfunction. Brain research bulletin 6 39236791
2022 Multiple Phosphorylations of SR Protein SRSF3 and Its Binding to m6A Reader YTHDC1 in Human Cells. Cells 6 35563766