Affinage

YTHDC1

YTH domain-containing protein 1 · UniProt Q96MU7

Length
727 aa
Mass
84.7 kDa
Annotated
2026-06-11
100 papers in source corpus 43 papers cited in narrative 43 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

YTHDC1 is the principal nuclear reader of N6-methyladenosine (m6A), using a conserved aromatic cage to selectively recognize a 5'-GG(m6A)C consensus through a binding pocket unique among YTH-domain proteins (PMID:25242552, PMID:26318451). High-resolution structural and biophysical work resolved the recognition mechanism in atomic detail: m6A is captured by the aromatic cage with cation-π-π stabilization of flanking nucleotides and water-mediated contacts that enforce the guanosine preference, and recognition of structured substrates requires local unfolding of RNA hairpins to present m6A in a single-stranded conformation (PMID:31670957, PMID:34258996, PMID:35166835). The same domain binds N6-methyladenine in single-stranded DNA with even higher affinity and reads damage-induced N1-methyladenosine, extending YTHDC1's reach beyond mRNA (PMID:32663306, PMID:40037355). Functionally, YTHDC1 governs multiple steps of nuclear RNA metabolism: it controls alternative splicing by recruiting SRSF3 while excluding SRSF10 from target transcripts (PMID:26876937), directs nuclear export of m6A-marked mRNAs via SRSF3 and NXF1 (PMID:28984244), and shapes alternative polyadenylation by interacting with 3'-end processing factors FIP1L1 and CPSF6 and antagonizing CPSF recruitment, a function coupled to m6A-driven liquid-liquid phase separation (PMID:29799838, PMID:36094741). These activities are physiologically essential, as conditional knockouts cause defects in gametogenesis, embryonic stem cell identity, satellite-cell and muscle stem-cell proliferation, and cardiac sarcomere integrity, with splicing rescued only by m6A-binding-competent protein (PMID:29799838, PMID:33658714, PMID:34716659, PMID:36892464, PMID:36722312). Through m6A reading of retrotransposon and LINE1 RNAs, YTHDC1 scaffolds SETDB1- and KAP1-mediated H3K9me3 to silence transposable elements and the 2C program (PMID:33658714, PMID:33886094). YTHDC1 additionally executes m6A-independent functions: it promotes TopBP1-MRE11-ATR-mediated DNA damage repair (PMID:38177310), drives transcriptional elongation at TP53 and DNA-damage-response loci (PMID:38951610), and stabilizes PPARγ by shielding it from ARIH2-mediated degradation via its intrinsically disordered region (PMID:40355558). Its activity is tuned by post-translational modification, including tyrosine phosphorylation that disperses it from nuclear YT bodies (PMID:10973987, PMID:15175272), O-GlcNAcylation at Ser396 promoting DNA-damage condensates (PMID:40242544), and K82 lactylation that enhances phase separation to protect oncogenic transcripts from the PAXT-exosome (PMID:40680722). YTHDC1 is required for AML leukemia stem-cell self-renewal and is an actionable target, with structure-guided inhibitors validated against AML cells (PMID:34255814, PMID:38787793).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1998 Low

    Established YTHDC1 (YT521) as a nuclear protein physically associated with splicing machinery, first hinting at a role in RNA processing before any reader function was known.

    Evidence Yeast two-hybrid and Far Western showing interaction with splicing factors SC35 and SF2

    PMID:9473574

    Open questions at the time
    • Single-lab identification by indirect binding only
    • No functional splicing assay
    • No m6A connection established
  2. 1999 High

    Showed YTHDC1 acts as a dose-dependent splicing regulator within a signaling-responsive nuclear interaction network, placing it downstream of kinase control.

    Evidence Co-IP, yeast two-hybrid, in vivo splicing assays with Sam68 and SAF-B; p59(fyn) phosphorylation of Sam68 dissolves nuclear dots

    PMID:10564280

    Open questions at the time
    • Mechanism of splice-site selection not defined
    • m6A dependence not yet known
  3. 2000 High

    Defined the subnuclear architecture and cell-cycle dynamics of YTHDC1, revealing it organizes into transcription-associated YT bodies requiring its low-complexity termini.

    Evidence Fluorescence microscopy, cell-cycle synchronization, deletion mapping, actinomycin D treatment

    PMID:10973987

    Open questions at the time
    • Functional role of YT bodies in splicing not resolved
    • Relationship to later phase-separation behavior not yet linked
  4. 2004 High

    Identified tyrosine phosphorylation as a regulatory switch controlling YTHDC1 localization and splicing activity, connecting kinase signaling to its nuclear function.

    Evidence Kinase assays (c-Abl, c-Src, p59(fyn)), phosphosite mapping, fractionation, in vivo splicing of IL-4R/CD44/SRp20

    PMID:15175272

    Open questions at the time
    • Phosphosites not mapped to structure
    • Interplay with m6A binding not addressed
  5. 2014 High

    Solved the structural basis of m6A recognition, defining YTHDC1 as a sequence-selective m6A reader via an aromatic cage and a unique 5' nucleotide pocket.

    Evidence X-ray crystallography of YTH-m6A RNA complex, binding assays, PAR-CLIP-seq

    PMID:25242552

    Open questions at the time
    • Functional consequences of binding not yet connected to splicing/export
    • Did not address water networks or hairpin substrates
  6. 2015 High

    Confirmed that YTHDC1's selectivity for the 5'-GGm6AC motif is unique among YTH proteins, distinguishing it mechanistically from cytoplasmic readers.

    Evidence Comparative crystallography of YTHDF1/Pho92 YTH domains and ITC

    PMID:26318451

    Open questions at the time
    • Did not establish in-cell functional divergence
    • Substrate context (hairpin vs single-strand) unaddressed
  7. 2016 High

    Defined YTHDC1's primary nuclear function as an m6A-dependent splicing regulator that recruits SRSF3 and excludes SRSF10 to promote exon inclusion.

    Evidence PAR-CLIP-seq, competitive in vitro pull-down, RNA-seq, m6A-binding-mutant reconstitution

    PMID:26876937

    Open questions at the time
    • Genome-wide rules for SRSF3 vs SRSF10 outcomes incomplete
    • Did not connect to export
  8. 2017 High

    Extended YTHDC1 function to nuclear export of m6A mRNAs and to SAM-responsive mRNA stability, establishing it as a multifunctional hub of m6A-dependent RNA fate.

    Evidence Knockdown with fractionation, m6A-seq, co-IP with SRSF3/NXF1; METTL16 reconstitution and MAT2A stability assays

    PMID:28984244 PMID:29262316

    Open questions at the time
    • Mechanism coupling splicing to export not fully integrated
    • Selectivity of export targets unresolved
  9. 2018 High

    Demonstrated in vivo physiological essentiality in gametogenesis and revealed YTHDC1 controls alternative polyadenylation in addition to splicing via 3'-end factors.

    Evidence Conditional knockout mouse, RNA-seq, m6A-seq, co-IP with CPSF6/SRSF3/SRSF7, m6A-mutant rescue

    PMID:29799838

    Open questions at the time
    • Direct molecular mechanism of APA control not yet defined
    • Tissue-specific target spectrum incomplete
  10. 2021 High

    Established YTHDC1 as an upstream organizer of heterochromatin, reading m6A on retrotransposon and LINE1 RNAs to scaffold SETDB1/KAP1-mediated H3K9me3 and maintain stem-cell identity.

    Evidence Conditional ESC knockouts, RNA-seq, ChIP-seq, RIP/LACE-seq, epistasis with SETDB1 and NCL/KAP1 co-IP

    PMID:33658714 PMID:33886094

    Open questions at the time
    • How RNA scaffolds direct chromatin writers spatially unresolved
    • Direct vs indirect chromatin recruitment not fully separated
  11. 2021 High

    Resolved the energetic and dynamic determinants of m6A recognition, identifying gating residues and structured water as contributors to specificity and affinity.

    Evidence Site-directed mutagenesis, ITC, NMR, MD simulations and free-energy calculations

    PMID:31670957 PMID:33472367 PMID:34258996

    Open questions at the time
    • In-cell relevance of water-mediated specificity untested
    • Did not address DNA substrates
  12. 2021 High

    Linked YTHDC1 to disease-relevant gene regulation, including AML leukemia stem-cell self-renewal via MCM4 and tissue-specific splicing controlling cardiac sarcomere integrity.

    Evidence In vivo AML genetic deletion with MeRIP-seq (MCM4); cardiac-specific knockout with m6A/RIP/RNA-seq (Titin)

    PMID:34255814 PMID:34716659

    Open questions at the time
    • Therapeutic window between LSC and HSC dependence narrow but mechanism incomplete
    • Causal contribution of each target not isolated
  13. 2020 High

    Showed the YTH domain reads N6-methyladenine in single-stranded DNA with high affinity, broadening YTHDC1's substrate repertoire beyond RNA.

    Evidence Two crystal structures of YTH-N6mA ssDNA complexes with FP/ITC binding

    PMID:32663306

    Open questions at the time
    • Biological role of DNA binding not demonstrated in this work
    • In-cell N6mA targets unknown
  14. 2022 High

    Mechanistically defined YTHDC1's control of alternative polyadenylation through direct FIP1L1 interaction and m6A-driven phase separation, and uncovered context-dependent splicing switching by AURKA.

    Evidence Co-IP (FIP1L1), APA-seq, FRAP/phase-separation assays; AURKA-driven SRSF3-to-hnRNPK switch by co-IP/RIP/minigene

    PMID:35361747 PMID:35966596 PMID:36094741

    Open questions at the time
    • Determinants selecting splicing vs APA vs export outcomes unresolved
    • AURKA switch validated in single context
  15. 2023 High

    Resolved how YTHDC1 reads structured RNA, showing recognition requires local unfolding of hairpins to expose m6A to the aromatic cage.

    Evidence NMR solution structure, X-ray crystallography, fluorescence-quenching binding assay

    PMID:35166835

    Open questions at the time
    • Kinetics of unfolding-coupled binding in cells unknown
    • Generality across natural hairpin contexts untested
  16. 2023 High

    Established YTHDC1 as a key regulator of stem-cell proliferation programs through m6A-dependent splicing and export feeding into PI4K-Akt-mTOR signaling, with new partners hnRNPG and DDX5.

    Evidence Inducible satellite-cell and muscle-stem-cell knockouts, LACE-seq/RIP, splicing analysis, phospho-signaling; co-IP with hnRNPG and DDX5 (circRNA biogenesis)

    PMID:36722312 PMID:36892464 PMID:37019933

    Open questions at the time
    • How partner selection is governed unclear
    • circRNA back-splicing role validated in single tumor context
  17. 2024 High

    Defined a genome-protective role: YTHDC1 reads damage-induced m1A/m6A and cooperates with the THO complex and DDX41-METTL3 to prevent RNA-damage-induced R-loops and DNA breaks.

    Evidence CRISPR-KO epistasis with THOC and XPG, RNA dealkylase rescue, R-loop detection; DDX41 KO/KI with METTL3-YTHDC1 co-IP

    PMID:38514771 PMID:40037355

    Open questions at the time
    • How m1A reading is structurally accommodated incompletely defined
    • DDX41 recruitment mechanism shown in single lab
  18. 2024 High

    Distinguished m6A-independent activities of YTHDC1 in genome maintenance and transcription, including TopBP1-MRE11-ATR repair and TP53 transcriptional elongation.

    Evidence Conditional KO and m6A-binding-mutant analysis, co-IP (TopBP1-MRE11), ATR assays; CRISPR screen, ChIP at TSS, intron-retention analysis

    PMID:38177310 PMID:38951610

    Open questions at the time
    • Structural basis of m6A-independent protein scaffolding unknown
    • How one protein partitions between RNA-reading and protein-scaffold roles unclear
  19. 2024 High

    Identified O-GlcNAcylation at Ser396 as a DNA-damage-responsive modification driving YTHDC1 chromatin recruitment, condensate formation, and HR repair.

    Evidence Site mutagenesis, RIP, FRAP, Rad51 foci and HR assays

    PMID:40242544

    Open questions at the time
    • Enzyme adding/removing O-GlcNAc not defined here
    • Interplay with other PTMs unresolved
  20. 2025 High

    Revealed PTM-controlled phase separation as a regulatory layer, with K82 lactylation expanding nuclear condensates to protect oncogenic transcripts from PAXT-exosome degradation, and an IDR-mediated m6A-independent protection of PPARγ.

    Evidence Lactylome analysis, K82 mutagenesis, p300 modulation, FRAP, PAXT-exosome and RNA-stability assays; BAT conditional KO with YTHDC1-PPARγ/ARIH2 co-IP and domain mapping

    PMID:40355558 PMID:40680722

    Open questions at the time
    • How condensate composition selects protected transcripts unclear
    • Relationship between lactylation, O-GlcNAcylation, and phosphorylation not integrated
  21. 2024 High

    Demonstrated YTHDC1 druggability with structure-guided, reader-selective inhibitors showing target engagement and antiproliferative activity in AML.

    Evidence Structure-based design with 1.6 Å crystal structure, CETSA, selectivity panel, AML antiproliferation; EPZ-5676 docking/biochemical inhibition in B-ALL

    PMID:38787793 PMID:39501105

    Open questions at the time
    • In vivo efficacy and safety not established
    • Whether inhibition blocks m6A-independent functions unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how YTHDC1 partitions a single small reader domain and intrinsically disordered region among its many parallel roles—splicing, export, APA, heterochromatin scaffolding, DNA repair, and transcription—and how the combinatorial PTM and phase-separation code selects which outcome and which transcripts dominate in a given cellular context.
  • No unified model linking PTMs, condensates, and functional output
  • Selectivity rules for partner and target choice undefined
  • In vivo therapeutic consequences of disrupting individual functions unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 5 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3 GO:0003677 DNA binding 2 GO:0140110 transcription regulator activity 1
Localization
GO:0005634 nucleus 3 GO:0005654 nucleoplasm 3 GO:0000228 nuclear chromosome 2
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-73894 DNA Repair 3 R-HSA-8953854 Metabolism of RNA 3 R-HSA-4839726 Chromatin organization 2 R-HSA-74160 Gene expression (Transcription) 1
Partners
DDX5FIP1L1METTL3NXF1PPARGSRSF10SRSF3TOPBP1

Evidence

Reading pass · 43 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 binding; YTHDC1 preferentially recognizes GG(m6A)C sequences through an aromatic cage, with a distinctly selective binding pocket for the nucleotide preceding m6A that is absent in other YTH family members. X-ray crystallography, biochemical binding assays, transcriptome-wide PAR-CLIP-seq Nature chemical biology High 25242552
2015 Structural comparison of YTH domain proteins revealed that only YTHDC1 harbors a distinctly selective binding pocket for the nucleotide preceding the m6A modification; all YTH domains use a conserved aromatic cage to recognize m6A, but YTHDC1's selectivity for 5'-GGm6AC is unique. X-ray crystallography of YTHDF1 and yeast Pho92 YTH domains in complex with m6A RNA, isothermal titration calorimetry binding assays The Journal of biological chemistry High 26318451
1999 YTHDC1 (YT521-B) interacts with Sam68 and scaffold attachment factor B in nuclear dots; the C-terminal glutamic acid/arginine-rich region mediates protein-protein interactions; Src family kinase p59(fyn)-mediated tyrosine phosphorylation of Sam68 negatively regulates its association with YT521-B and dissolves nuclear dots; overexpression of YT521-B modulates alternative splice site selection in a concentration-dependent manner in vivo. Co-immunoprecipitation, yeast two-hybrid, in vivo splicing assays, immunofluorescence, kinase overexpression Molecular biology of the cell High 10564280
2000 YTHDC1 (YT521-B) localizes to a novel subnuclear structure (YT bodies) that first appears at the beginning of S-phase and disperses during mitosis; YT bodies contain transcriptionally active sites and are in close contact with speckles and coiled bodies; actinomycin D disperses YT bodies; the N-terminal glutamic acid-rich domain and C-terminal glutamic acid/arginine-rich region are required for YT body formation. Fluorescence microscopy, cell cycle synchronization, deletion analysis, transcriptional inhibitor treatment The Journal of cell biology High 10973987
2003 YTHDC1 (YT521-B) interacts directly with emerin (a nuclear membrane protein) via a bipartite binding site in emerin; this interaction inhibits YT521-B-dependent splice site selection in vivo, suggesting emerin regulates splicing through YTHDC1. Yeast two-hybrid, pull-down assay, BIAcore biomolecular interaction analysis, in vivo splicing assay, alanine substitution mutagenesis European journal of biochemistry Medium 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 YT521-B from YT bodies to an insoluble nucleoplasmic form; phosphorylation by c-Abl abolishes the concentration-dependent effect of YT521-B on alternative splice site selection of IL-4 receptor, CD44, and SRp20. Kinase assay, phosphorylation site mapping, subcellular fractionation, in vivo splicing assay, immunofluorescence Human molecular genetics High 15175272
1998 YTHDC1 (YT521) was identified as an RA301-binding protein via yeast two-hybrid; Far Western blot showed YT521 protein interacts with splicing factors SC35 and SF2, suggesting a role in RNA splicing. Yeast two-hybrid, Far Western blot Brain research. Molecular brain research Low 9473574
2016 Nuclear m6A reader YTHDC1 promotes exon inclusion by recruiting splicing factor SRSF3 while blocking SRSF10 binding to target mRNAs; YTHDC1 facilitates SRSF3 and represses SRSF10 in nuclear speckle localization and RNA-binding affinity; these effects require m6A-binding ability of YTHDC1 as shown by reconstitution with wild-type but not m6A-binding-defective YTHDC1. PAR-CLIP-seq, in vitro pull-down assay showing competitive SRSF3/SRSF10 binding, RNA-seq transcriptome analysis, knockdown/reconstitution with wild-type vs. m6A-binding-defective YTHDC1 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; YTHDC1 interacts with SRSF3 and NXF1 and facilitates RNA binding to both. YTHDC1 knockdown with nuclear/cytoplasmic fractionation, m6A-seq, co-immunoprecipitation with SRSF3 and NXF1, RNA binding assays eLife High 28984244
2017 YTHDC1 reads m6A marks deposited by METTL16 in the 3' UTR of MAT2A mRNA; in response to SAM depletion, YTHDC1 and METTL16 together mediate SAM-responsive regulation of MAT2A mRNA stability; knockdown of YTHDC1 abolishes this regulation. In vitro methylation assay with recombinant METTL16, YTHDC1 knockdown, mutagenesis of METTL16 target adenines in 3' UTR, mRNA stability assay Cell reports High 29262316
2018 YTHDC1 is essential for spermatogonial development and oocyte growth/maturation in mice; loss of YTHDC1 causes extensive alternative polyadenylation (altering 3' UTR length) and massive alternative splicing defects in oocytes; YTHDC1 associates with 3' end processing factors CPSF6, SRSF3, and SRSF7; splicing defects are rescued by wild-type but not m6A-binding-deficient YTHDC1. Conditional knockout mouse model, RNA-seq, m6A sequencing, co-immunoprecipitation with CPSF6/SRSF3/SRSF7, rescue with wild-type vs. m6A-binding-deficient YTHDC1 PLoS genetics High 29799838
2019 Atomistic simulations, X-ray crystallography, and isothermal titration calorimetry showed that m6A is captured by an aromatic cage of YTHDC1; 3' terminus nucleotides are stabilized by cation-π-π interactions; the 5' terminus remains flexible; the methyl group of m6A shifts conformational preferences of the oligoribonucleotide to a bound-like conformation facilitating association. Atomistic molecular dynamics simulations, X-ray crystallography, isothermal titration calorimetry Journal of chemical theory and computation High 31670957
2019 Metadherin interacts with YTHDC1, Sam68, and T-STAR in nuclear speckles and influences splice site selection in a dose-dependent manner in CD44v5-luc minigene reporter assays. Yeast two-hybrid, co-immunoprecipitation, minigene splicing reporter assay Cancers Medium 31450747
2020 The YTH domain of YTHDC1 binds N6-methyladenine in single-stranded DNA with ~10 nM Kd, stronger than its affinity for N6-methyladenosine RNA; crystal structures of YTHDC1 YTH domain bound to N6mA-containing ssDNA show methylated adenine binding in a single-stranded region flanked by duplexed DNA. X-ray crystallography (two structures), fluorescence polarization/ITC binding assays Nucleic acids research High 32663306
2021 YTHDC1 is required for maintenance of mouse ES cell identity in an m6A-dependent manner; depletion initiates reprogramming to a 2C-like state; YTHDC1 binds transcripts of retrotransposons (IAPs, ERVK, LINE1) and its depletion causes reactivation of silenced retrotransposons 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 in mouse ESCs, RNA-seq, ChIP-seq (H3K9me3), RIP-seq, epistasis analysis with SETDB1 Nature High 33658714
2021 YTHDC1 recognizes m6A on LINE1 RNAs in the nucleus and regulates formation of the LINE1-nucleolin (NCL) partnership and chromatin recruitment of KAP1; Ythdc1 depletion interrupts H3K9me3 establishment on 2C-related retrotransposons in ESCs and inner cell mass cells, increasing transcriptional activity of the 2C program. Conditional knockout in ESCs, LACE-seq, ChIP-seq, RIP, Co-IP (YTHDC1-NCL, YTHDC1-KAP1) Protein & cell High 33886094
2021 YTHDC1 regulates leukemogenesis through MCM4, a critical regulator of DNA replication; YTHDC1 is required for proliferation and survival of AML cells and self-renewal of leukemia stem cells in vivo; Ythdc1 haploinsufficiency reduces LSC but not HSC self-renewal. Genetic deletion of Ythdc1 in mouse AML models, YTHDC1 knockdown in primary AML cells, RNA-seq, m6A-MeRIP-seq identifying MCM4 as target Blood High 34255814
2021 YTHDC1 binds SQSTM1 mRNA in the nucleus and cooperates with ELAVL1/HuR to modulate its stability; knockdown of YTHDC1 drives SQSTM1 mRNA degradation in the nucleus, causing blockade of autophagic flux in keratinocytes. RIP assay (YTHDC1 binding to SQSTM1 mRNA), co-immunoprecipitation (YTHDC1-ELAVL1), YTHDC1 knockdown/overexpression, autophagic flux assays Autophagy Medium 34657574
2021 YTHDC1 facilitated the biogenesis of mature miR-30d via m6A-mediated regulation of mRNA stability in pancreatic cancer cells. RIP, MeRIP, RNA stability assay, YTHDC1 knockdown Cell death and differentiation Low 34021267
2021 YTHDC1 regulates splicing of Titin mRNA via m6A modification; cardiac-specific Ythdc1 knockout leads to aberrant Titin splicing, disordered sarcomere arrangement, and dilated cardiomyopathy in mice. Cardiac-specific conditional Ythdc1 knockout, m6A-MeRIP-seq, RIP-seq, mRNA-seq, integrated target identification Journal of cellular and molecular medicine High 34716659
2021 In HIV-1 producer cells, YTHDC1 binds HIV-1 transcripts in a METTL3-dependent manner and controls unspliced/incompletely spliced HIV-1 RNA levels; YTHDC1 knockdown reduces Env and Vpu expression and leads to incorporation of unprocessed Env gp160 into viral particles, decreasing infectivity. YTHDC1 knockdown, RIP assay, RT-qPCR for HIV-1 RNA species, Western blot for viral proteins Journal of virology Medium 33883220
2021 Site-directed mutagenesis and atomistic simulations identified four residues (Trp428, Met438, Ser378, Thr379) regulating m6A binding; Trp428 switches between two states to build/dismantle the aromatic cage; a structural water molecule synergistically binds YTHDC1 with m6A as a hydrogen-bond hub; Thr379Val significantly impairs binding and thermal stability. Site-directed mutagenesis, isothermal titration calorimetry, molecular dynamics simulations, free energy calculations Journal of chemical theory and computation High 33472367
2021 NMR and MD simulations showed that structured water molecules surrounding the bound RNA and the methylated substrate's ability to exclude bulk water contribute to YTHDC1's preference for m6A; the D479A mutant disrupts a water network and destabilizes m6A binding; YTHDC1's 5'-Gm6A-3' motif preference is partially facilitated by water-mediated interactions with the guanosine 2-amino group. Molecular dynamics simulations, NMR spectroscopy, isothermal titration calorimetry, site-directed mutagenesis (D479A) The journal of physical chemistry. B High 34258996
2022 NMR solution structure of the (m6A)UCG hairpin and crystal structure of YTHDC1 bound to it revealed that YTHDC1 recognizes the (m6A)UC nucleotides in a single-stranded conformation by inserting m6A into the aromatic cage; recognition requires local unfolding of the upper stem region of the hairpin, shown by NMR and fluorescence quenching. NMR spectroscopy (solution structure), X-ray crystallography, fluorescence quenching binding assay Nucleic acids research High 35166835
2022 Nuclear AURKA disrupts the binding of SRSF3 to YTHDC1 and recruits hnRNP K to YTHDC1 in a kinase-independent manner, switching from m6A-YTHDC1-SRSF3-mediated exon inclusion of RBM4-FL to m6A-YTHDC1-hnRNPK-dependent exon skipping to produce the short RBM4-S isoform that promotes lung cancer progression. Co-immunoprecipitation, RIP, RNA-seq, AURKA nuclear translocation experiments, minigene splicing assay Signal transduction and targeted therapy Medium 35361747
2022 YTHDC1 suppresses proximal alternative polyadenylation (APA) sites by binding upstream m6A sites; YTHDC1 directly interacts with 3' end processing factor FIP1L1 and interferes with FIP1L1's ability to recruit CPSF4; m6A binding promotes liquid-liquid phase separation of YTHDC1 and FIP1L1. m6A-seq, APA analysis, co-immunoprecipitation (YTHDC1-FIP1L1), FRAP/phase separation assay, YTHDC1 knockdown EMBO reports High 36094741
2022 YTHDC1 promotes nuclear export of SMAD3 mRNA in an m6A-dependent manner; YTHDC1 depletion causes nuclear retention of SMAD3 mRNA and reduced SMAD3 protein, impairing TGF-β-induced EMT and TNBC cell migration/invasion; m6A-binding defective YTHDC1 mutant cannot rescue the phenotype. RNA-seq, m6A-seq, RIP-seq, nuclear/cytoplasmic fractionation of SMAD3 mRNA, YTHDC1 KO with SMAD3 overexpression rescue, m6A-binding mutant Theranostics High 35966596
2023 YTHDC1 is an essential regulator of skeletal muscle satellite cell (SC) activation and proliferation; transcriptome-wide LACE-seq identified m6A-mediated binding targets; YTHDC1 regulates splicing and nuclear export of target mRNAs; hnRNPG was identified as a bona fide interacting partner of YTHDC1 in myoblasts. Inducible YTHDC1 depletion in satellite cells, LACE-seq, splicing analysis, nuclear export analysis, interactome mapping, co-IP (hnRNPG) eLife High 36892464
2023 The m6A reader YTHDC1 interacts with DDX5 RNA helicase; YTHDC1 and DDX5 together promote production of a common subset of circRNAs via back-splicing in rhabdomyosarcoma, and their depletion reduces RMS cell proliferation. Co-immunoprecipitation (YTHDC1-DDX5), circRNA-seq, YTHDC1/DDX5 knockdown, proliferation assays Nature communications Medium 37019933
2023 YTHDC1 promotes muscle stem cell proliferation via PI4K-Akt-mTOR signalling; Ythdc1 binds m6A-modified Pi4k2a and Pi4kb mRNAs and regulates their alternative splicing, thus controlling PI4K-Akt-mTOR signalling; Ythdc1-null muscle stem cells show deficiency in PIP3, phospho-Akt, and phospho-S6. Inducible Ythdc1 knockout in muscle stem cells, RIP (Pi4k2a, Pi4kb binding), splicing analysis, phospho-signaling Western blot Cell proliferation High 36722312
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, increasing FSP1 protein and ferroptosis resistance in lung cancer. RIP (YTHDC1-FSP1 mRNA), Co-IP (YTHDC1-CSTF3, FSP1-HuR), APA analysis, RNA stability assay, YTHDC1 knockdown Cell death and differentiation Medium 37903990
2023 YTHDC1 promotes IAV replication by binding to influenza A virus NS segment m6A sites at the NS 3' splicing site and inhibiting NS mRNA splicing, thereby promoting viral replication and pathogenicity in vitro and in vivo. YTHDC1 knockdown/overexpression, m6A mapping on NS RNA, RIP assay, splicing assay, in vivo infection model PLoS pathogens Medium 37053288
2023 YTHDC1 delays stress-induced pulmonary senescence and fibrosis in an m6A-independent manner by promoting interaction between TopBP1 and MRE11, thereby activating ATR and facilitating DNA damage repair; m6A-binding-defective YTHDC1 retains this function. Ythdc1 conditional KO mice, YTHDC1 overexpression with m6A-binding mutant, co-immunoprecipitation (TopBP1-MRE11 interaction), ATR activation assay The EMBO journal High 38177310
2023 YTHDC1 positively regulates PTEN expression by stabilizing PTEN mRNA in an m6A-dependent manner; YTHDC1 knockdown destabilizes PTEN mRNA and activates PI3K/AKT signaling, promoting cisplatin resistance in bladder cancer. RIP assay (YTHDC1-PTEN mRNA), RNA stability assay, YTHDC1 knockdown/overexpression, qPCR, Western blot Cell proliferation Medium 37070134
2024 YTHDC1 cooperates with the THO complex (THOC) to prevent RNA-damage-induced DNA breaks (RDIBs); YTHDC1 binds to chemically induced N1-methyladenosine (m1A) in addition to m6A; without YTHDC1, alkylation-damaged RNA forms R-loops that are converted to DNA breaks by XPG nuclease; a nuclear RNA m1A methyltransferase is sufficient to induce DNA breaks in the absence of YTHDC1 or THOC. CRISPR-KO of YTHDC1 and THOC, comet assay, DNA break quantification, RNA dealkylase rescue experiment, R-loop detection, XPG nuclease epistasis Molecular cell High 40037355
2024 YTHDC1 m6A-binding activity promotes transcriptional elongation at the TP53 locus and other DNA damage response genes, and prevents intron retention in key DDR factors; TP53 transcriptional pause-release by YTHDC1 is independent of m6A; YTHDC1 deficiency causes genomic instability and aberrant cancer cell proliferation. CRISPR-KO screen identifying YTHDC1 in p53 response, m6A binding mutant analysis, intron retention analysis, ChIP (YTHDC1 at transcription start sites), RNA-seq The EMBO journal High 38951610
2024 DDX41 promotes the recruitment of YTHDC1 to R-loops by promoting binding between METTL3 and YTHDC1; DDX41 KO/KI cells show impaired METTL3-YTHDC1 interaction and increased m6A-methylated R-loops, leading to genomic instability. DDX41 KO and knock-in cell lines, Co-IP (DDX41-METTL3, METTL3-YTHDC1), m6A quantification, R-loop detection, primary patient samples Leukemia Medium 38514771
2024 YTHDC1 is O-GlcNAcylated at Ser396 upon DNA damage, which is required for YTHDC1 chromatin binding, IRIF formation, and m6A RNA binding at DNA damage sites; O-GlcNAcylation promotes YTHDC1 condensate formation and HR-mediated DNA repair and Rad51 recruitment. Site-directed mutagenesis (Ser396), RIP showing O-GlcNAc-dependent m6A binding, FRAP analysis of condensate formation, Rad51 foci quantification, HR assay Fundamental research High 40242544
2024 YTHDC1 binds to and stabilizes m6A-modified KMT2C mRNA; KMT2C catalyzes H3K4 methylation required for DDR gene expression; YTHDC1 knockdown increases DNA damage in B-ALL cells; EPZ-5676 was identified as a YTHDC1 inhibitor by molecular docking and biochemical experiments. RIP (YTHDC1-KMT2C mRNA), ChIP-seq (H3K4me1/me3), RNA stability assay, molecular docking, biochemical YTHDC1 inhibitor assay, B-ALL xenograft Leukemia Medium 39501105
2024 Structure-based design produced YTHDC1 inhibitor compound 40 (Kd = 49 nM); crystal structure at 1.6 Å validated the binding mode; compound 40 is selective against cytoplasmic YTH readers and shows antiproliferative activity in AML cell lines; cellular thermal shift assay confirmed target engagement. X-ray crystallography (1.6 Å), biochemical binding assay, selectivity panel, cellular thermal shift assay, AML cell antiproliferative assay Journal of medicinal chemistry High 38787793
2025 YTHDC1 is lactylated at K82 by p300 under hypoxia; K82 lactylation (YTHDC1K82la) increases YTHDC1 phase separation and nuclear condensate expansion, protecting oncogenic transcripts BCL2 and E2F2 from degradation by the PAXT-exosome complex in renal cell carcinoma cells. Lactylome analysis, site-directed mutagenesis (K82), p300 inhibition/overexpression, FRAP phase separation assay, RNA stability assay, PAXT-exosome interaction Molecular cell High 40680722
2025 YTHDC1 directly interacts with PPARγ through its intrinsically disordered region (IDR) and protects PPARγ from ARIH2 E3 ubiquitin ligase-mediated proteasomal degradation, in an m6A-independent manner; deletion of Ythdc1 in brown adipose tissue increases PPARγ degradation, impairing interscapular BAT development and thermogenesis. Conditional Ythdc1 KO in BAT, co-immunoprecipitation (YTHDC1-PPARγ, ARIH2-PPARγ), domain mapping (YTHDC1 IDR, PPARγ A/B domain), proteasomal degradation assay, energy expenditure measurements The EMBO journal High 40355558
2024 YTHDC1 interacts with HP1BP3 (a nuclear RNA-binding protein); YTHDC1 deficiency causes significant alterations in microRNA levels and HSC apoptosis; overexpression of mir-125b, mir-99b, and let-7e partially rescues functional defects of YTHDC1-null HSCs, indicating YTHDC1 regulates HSC maintenance via HP1BP3-dependent microRNA maturation. Conditional Ythdc1 KO and Ythdc1/Mettl3 double KO mice, co-IP (YTHDC1-HP1BP3), small RNA-seq, miRNA rescue experiments Cell death discovery High 39414764

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 1700 26876937
2017 YTHDC1 mediates nuclear export of N6-methyladenosine methylated mRNAs. eLife 1052 28984244
2014 Structural basis for selective binding of m6A RNA by the YTHDC1 YTH domain. Nature chemical biology 595 25242552
2018 Nuclear m6A reader YTHDC1 regulates alternative polyadenylation and splicing during mouse oocyte development. PLoS genetics 463 29799838
2021 The RNA m6A reader YTHDC1 silences retrotransposons and guards ES cell identity. Nature 302 33658714
2017 S-Adenosylmethionine Synthesis Is Regulated by Selective N6-Adenosine Methylation and mRNA Degradation Involving METTL16 and YTHDC1. Cell reports 302 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.) 166 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 153 34021267
2021 m6A reader YTHDC1 modulates autophagy by targeting SQSTM1 in diabetic skin. Autophagy 150 34657574
2021 Nuclear m6A reader YTHDC1 regulates the scaffold function of LINE1 RNA in mouse ESCs and early embryos. Protein & cell 140 33886094
2021 A critical role of nuclear m6A reader YTHDC1 in leukemogenesis by regulating MCM complex-mediated DNA replication. Blood 132 34255814
2016 Nuclear m(6)A Reader YTHDC1 Regulates mRNA Splicing. Trends in genetics : TIG 124 27050931
2021 The multifaceted effects of YTHDC1-mediated nuclear m6A recognition. Trends in genetics : TIG 98 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 74 37903990
2023 Nuclear m6A reader YTHDC1 promotes muscle stem cell activation/proliferation by regulating mRNA splicing and nuclear export. eLife 65 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 61 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 61 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 56 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 53 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 47 37070134
2024 NAT10 mediated ac4C acetylation driven m6A modification via involvement of YTHDC1-LDHA/PFKM regulates glycolysis and promotes osteosarcoma. Cell communication and signaling : CCS 44 38233839
2023 The m6A reader YTHDC1 and the RNA helicase DDX5 control the production of rhabdomyosarcoma-enriched circRNAs. Nature communications 44 37019933
2022 Structural effects of m6A modification of the Xist A-repeat AUCG tetraloop and its recognition by YTHDC1. Nucleic acids research 44 35166835
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 38 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
2024 Impaired binding affinity of YTHDC1 with METTL3/METTL14 results in R-loop accumulation in myelodysplastic neoplasms with DDX41 mutation. Leukemia 33 38514771
2023 The YTHDC1/GLUT3/RNF183 axis forms a positive feedback loop that modulates glucose metabolism and bladder cancer progression. Experimental & molecular medicine 32 37258572
2021 YTHDC1-mediated VPS25 regulates cell cycle by targeting JAK-STAT signaling in human glioma cells. Cancer cell international 32 34863175
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 31 37428639
2023 A potassium-chloride co-transporter promotes tumor progression and castration resistance of prostate cancer through m6A reader YTHDC1. Cell death & disease 30 36609444
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 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 28 35198364
2022 Nuclear m6 A reader YTHDC1 suppresses proximal alternative polyadenylation sites by interfering with the 3' processing machinery. EMBO reports 28 36094741
2022 Downregulation of the m6A reader protein YTHDC1 leads to islet β-cell failure and diabetes. Metabolism: clinical and experimental 28 36302453
2024 Histone lactylation-driven YTHDC1 promotes hepatocellular carcinoma progression via lipid metabolism remodeling. Cancer letters 26 39725144
2024 KIAA1429 facilitates metastasis via m6A-YTHDC1-dependent RND3 down-regulation in hepatocellular carcinoma cells. Cancer letters 24 38224863
2023 The m6A reader YTHDC1 regulates muscle stem cell proliferation via PI4K-Akt-mTOR signalling. Cell proliferation 24 36722312
2021 LINC00857 promotes cell proliferation and migration in colorectal cancer by interacting with YTHDC1 and stabilizing SLC7A5. Oncology letters 23 34122629
2025 YTHDC1 lactylation regulates its phase separation to enhance target mRNA stability and promote RCC progression. Molecular cell 22 40680722
2023 N6-methyladenosine reader protein YTHDC1 regulates influenza A virus NS segment splicing and replication. PLoS pathogens 22 37053288
2019 Flexible Binding of m6A Reader Protein YTHDC1 to Its Preferred RNA Motif. Journal of chemical theory and computation 22 31670957
2025 High-glucose-associated YTHDC1 lactylation reduces the sensitivity of bladder cancer to enfortumab vedotin therapy. Cell reports 21 40215164
2022 YTHDC1 regulates distinct post-integration steps of HIV-1 replication and is important for viral infectivity. Retrovirology 21 35101069
2021 Atomistic and Thermodynamic Analysis of N6-Methyladenosine (m6A) Recognition by the Reader Domain of YTHDC1. Journal of chemical theory and computation 21 33472367
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
2024 Structure-Based Design of a Potent and Selective YTHDC1 Ligand. Journal of medicinal chemistry 19 38787793
2023 Low expression of m6A reader YTHDC1 promotes progression of ovarian cancer via PIK3R1/STAT3/GANAB axis. International journal of biological sciences 18 37781028
2023 METTL3/YTHDC1-mediated upregulation of LINC00294 promotes hepatocellular carcinoma progression. Heliyon 17 38125436
2020 YTHDC1 gene polymorphisms and hepatoblastoma susceptibility in Chinese children: A seven-center case-control study. The journal of gene medicine 17 32729171
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 16 39501105
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
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 16 34258996
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 15 40221424
2023 YTHDC1 maintains trophoblasts function by promoting degradation of m6A-modified circMPP1. Biochemical pharmacology 15 36780989
2024 YTHDC1-dependent m6A modification modulated FOXM1 promotes glycolysis and tumor progression through CENPA in triple-negative breast cancer. Cancer science 14 38566554
2024 YTHDC1 aggravates high glucose-induced retinal vascular endothelial cell injury via m6A modification of CDK6. Biology direct 14 38978074
2023 SILENCING M 6 A READER YTHDC1 REDUCES INFLAMMATORY RESPONSE IN SEPSIS-INDUCED CARDIOMYOPATHY BY INHIBITING SERPINA3N EXPRESSION. Shock (Augusta, Ga.) 14 36877222
2025 YTHDC1 cooperates with the THO complex to prevent RNA-damage-induced DNA breaks. Molecular cell 13 40037355
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 Reduction of mRNA m6A associates with glucose metabolism via YTHDC1 in human and mice. Diabetes research and clinical practice 13 36878322
2021 YTHDC1 gene polymorphisms and neuroblastoma susceptibility in Chinese children. Aging 13 34897032
2025 piR-26441 inhibits mitochondrial oxidative phosphorylation and tumorigenesis in ovarian cancer through m6A modification by interacting with YTHDC1. Cell death & disease 12 39827178
2024 The METTL3-m6A-YTHDC1-AMIGO2 axis contributes to cell proliferation and migration in esophageal squamous cell carcinoma. Gene 11 38360124
2024 Mir22hg facilitates ferritinophagy-mediated ferroptosis in sepsis by recruiting the m6A reader YTHDC1 and enhancing Angptl4 mRNA stability. Journal of bioenergetics and biomembranes 11 38842666
2024 YTHDC1 m6A-dependent and m6A-independent functions converge to preserve the DNA damage response. The EMBO journal 11 38951610
2024 METTL3 mediates m6A modification of lncRNA CRNDE to promote ATG10 expression and improve brain ischemia/reperfusion injury through YTHDC1. Biology direct 11 39407279
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 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
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 10 36935054
2023 DNA damage-induced YTHDC1 O-GlcNAcylation promotes homologous recombination by enhancing m6A binding. Fundamental research 10 40242544
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 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.) 9 38995602
2024 YTHDC1 Regulates the Migration, Invasion, Proliferation, and Apoptosis of Rheumatoid Fibroblast-Like Synoviocytes. Frontiers in immunology 9 39534605
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 ALKBH5 facilitates tumor progression via an m6A-YTHDC1-dependent mechanism in glioma. Cancer letters 8 39761866
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 YTHDC1 inhibits autophagy-dependent NF-κB signaling by stabilizing Beclin1 mRNA in macrophages. Journal of inflammation (London, England) 8 38877444
2024 N6-methyladenosine demethylase FTO regulates neuronal oxidative stress via YTHDC1-ATF3 axis in arsenic-induced cognitive dysfunction. Journal of hazardous materials 8 39265400
2024 YTHDC1-mediated microRNA maturation is essential for hematopoietic stem cells maintenance. Cell death discovery 8 39414764
2023 The m6A reader YTHDC1-mediated lncRNA CTBP1-AS2 m6A modification accelerates cholangiocarcinoma progression. Heliyon 8 37809459
2023 Recruitment of PVT1 Enhances YTHDC1-Mediated m6A Modification of IL-33 in Hyperoxia-Induced Lung Injury During Bronchopulmonary Dysplasia. Inflammation 8 37917328
2025 YTHDC1 Modulates the Osteogenic Capacity of hPDLSCs via Wnt/β-Catenin Signalling Pathway for the Treatment of Bone Defects in Osteoporosis Rats. Cell proliferation 7 40097906
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 Functional role of lncRNA MEG3 on pyroptosis through interacting with EZH2 and YTHDC1 in postoperative cognitive dysfunction. Brain research bulletin 7 39236791
2021 YTHDC1 gene polymorphisms and Wilms tumor susceptibility in Chinese children: A five-center case-control study. Gene 7 33737126

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