Affinage

NAT10

RNA cytidine acetyltransferase · UniProt Q9H0A0

Length
1025 aa
Mass
115.7 kDa
Annotated
2026-04-29
100 papers in source corpus 39 papers cited in narrative 39 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NAT10 is a multifunctional acetyltransferase that serves as the primary writer of N4-acetylcytidine (ac4C) on tRNA, rRNA, and mRNA, and additionally acetylates diverse protein substrates, thereby integrating epitranscriptomic gene regulation with ribosome biogenesis, DNA damage repair, and chromatin organization. As an RNA acetyltransferase, NAT10 deposits ac4C on mRNA targets—recruited via adaptor proteins PCBP1/2 and TDP43—to stabilize transcripts and enhance translation efficiency, with validated targets spanning metabolic enzymes, signaling mediators, and cell-cycle regulators across immune, cardiac, germ-cell, and cancer contexts (PMID:37463108, PMID:39556689, PMID:40045031, PMID:39506072). NAT10 also acetylates protein substrates including p53 (K120), UBF, Che-1, DDX21, MORC2, PARP1, NPM1, and SRSF2 to regulate rRNA transcription, autophagy, R-loop resolution, DNA damage response, and pre-mRNA splicing; its intrinsic RecD helicase domain additionally unwinds nucleolar R-loops directly (PMID:26882543, PMID:27993683, PMID:30165671, PMID:39394182, PMID:39024555). NAT10 nucleocytoplasmic and nucleolar-nucleoplasmic shuttling is controlled by PARP1-mediated PARylation and Sirt1-mediated deacetylation, and its protein stability is regulated by USP39-mediated deubiquitination and Khib modification, with mislocalized cytoplasmic NAT10 acetylating α-tubulin to reorganize microtubules—an activity exploited therapeutically by the inhibitor Remodelin to rescue nuclear architecture in laminopathic cells (PMID:24786082, PMID:35986334, PMID:29634924, PMID:36882514).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2007 Medium

    The initial characterization of NAT10 (hALP) established it as a nuclear membrane-associated acetyltransferase with histone acetyltransferase activity linked to mitotic chromosome de-condensation, framing NAT10 as an acetylation enzyme with nuclear structural functions.

    Evidence HAT activity assays and co-localization with hsSUN1 at the inner nuclear membrane

    PMID:17631499

    Open questions at the time
    • HAT substrate specificity not defined beyond bulk histones
    • no connection to RNA acetylation yet established
    • mechanism linking HAT activity to chromosome de-condensation unclear
  2. 2014 High

    The discovery that Remodelin targets NAT10 to rescue nuclear shape defects in laminopathic and HGPS cells revealed NAT10 as a druggable regulator of nuclear architecture via microtubule reorganization, establishing its first disease-relevant function.

    Evidence Chemical-genetic screen identifying Remodelin, validated by siRNA knockdown and cellular rescue across multiple laminopathic cell types

    PMID:24786082

    Open questions at the time
    • direct acetyltransferase substrate mediating microtubule reorganization unknown at this point
    • mechanism linking NAT10 to microtubule dynamics not defined
  3. 2016 High

    Two studies established NAT10 as both a protein acetyltransferase acting on p53 (K120) and a self-regulating enzyme via autoacetylation at K426, connecting NAT10 to both the DNA damage/cell cycle checkpoint and rRNA transcription activation.

    Evidence In vitro acetylation assays, K426R mutagenesis abolishing UBF acetylation and rRNA transcription, nucleolar-to-nucleoplasmic translocation after DNA damage

    PMID:26882543 PMID:27993683

    Open questions at the time
    • E3 ligase activity toward Mdm2 reported in same study but not independently confirmed
    • how autoacetylation is regulated by upstream signals unknown
    • relationship between protein and RNA acetyltransferase activities not addressed
  4. 2018 High

    Multiple 2018 studies defined NAT10's regulatory logic: Sirt1-mediated deacetylation toggles NAT10 between rRNA biogenesis and autophagy via Che-1 acetylation, while nucleolar localization signals were mapped and shown to prevent cytoplasmic mislocalization that drives α-tubulin acetylation, and the HGPS rescue mechanism was traced to Transportin-1 nuclear-cytoplasmic rebalancing.

    Evidence Sirt1 deacetylation assays with autophagy/rRNA readouts; GFP-deletion mutant localization mapping; subcellular fractionation and nuclear import assays in HGPS cells

    PMID:29634924 PMID:29970603 PMID:30165671

    Open questions at the time
    • Sirt1-NAT10 axis not confirmed in vivo
    • whether tubulin acetylation by mislocalized NAT10 is direct or via ATAT1 unclear
    • full set of NAT10 NLS/NoLS not structurally resolved
  5. 2019 Medium

    Consolidation of evidence established NAT10 as an RNA acetyltransferase catalyzing ac4C on 18S rRNA, with roles in 40S ribosomal subunit assembly, linking its acetyltransferase activity to ribosome biogenesis beyond rDNA transcription.

    Evidence Review synthesizing biochemical and structural data from NAT10 and yeast ortholog Kre33

    PMID:31491951

    Open questions at the time
    • mRNA ac4C writing by NAT10 not yet demonstrated at this point
    • structural basis of RNA substrate recognition not resolved
    • adaptor proteins for RNA targeting unknown
  6. 2021 Medium

    NAT10-mediated ac4C modification was extended to mRNA substrates when ac4C of RUNX2 mRNA was shown to stabilize the transcript and promote osteogenic differentiation, establishing the mRNA stability paradigm for NAT10 epitranscriptomics.

    Evidence ac4C-RIP, mRNA half-life assays, NAT10 KD/OE in BMSCs, OVX mouse model

    PMID:34513300

    Open questions at the time
    • single mRNA target validated at this stage
    • mechanism by which ac4C stabilizes mRNA not defined
    • whether ac4C recruits reader proteins unknown
  7. 2022 High

    A burst of studies expanded NAT10's mRNA ac4C and protein acetylation repertoire: ac4C of ULK1 mRNA controls neutrophil inflammasome signaling, PARP1 PARylation at C-terminal lysines governs NAT10 nucleoplasmic translocation for MORC2 acetylation in DNA damage response, NAT10/DDX21 enhance RNase H1 endonuclease activity for R-loop resolution, and Khib at K823 stabilizes NAT10 via USP39. Germ cell-specific Nat10 knockout revealed essential roles in meiotic entry and recombination.

    Evidence ac4C-RIP, PARP1 PARylation reconstitution with K3A mutagenesis, BioID with in vitro RNase H1 cleavage assays, Khib MS profiling with mutagenesis, germ cell CKO with meiotic cytology

    PMID:35801907 PMID:35852833 PMID:35986334 PMID:36068299 PMID:36882514

    Open questions at the time
    • full spectrum of mRNA targets genome-wide still emerging
    • structural basis for PARP1-NAT10 interaction not resolved
    • whether NAT10 helicase and acetyltransferase activities are coordinated at R-loops unknown at this time
  8. 2023 High

    Studies in 2023 demonstrated that NAT10 ac4C modification sculpts the maternal transcriptome via CCR4-NOT-mediated poly(A) tail degradation, stabilizes oncogenic mRNAs (AHNAK, MDM2, NOTCH3), regulates tRNA ac4C to control translation efficiency of EGFR-enriched codons, and modifies KSHV PAN lncRNA to trigger viral lytic reactivation—collectively showing ac4C operates on tRNA, mRNA, and viral RNA to control diverse biological outputs.

    Evidence Oocyte CKO with poly(A) tail assay; acRIP-seq/ribosome profiling in ESCA; ac4C site mutagenesis in KSHV PAN RNA; multiple in vivo models

    PMID:36898834 PMID:36939377 PMID:37349316 PMID:37463108 PMID:37816771

    Open questions at the time
    • whether tRNA and mRNA ac4C are written by the same or distinct NAT10 complexes unknown
    • reader proteins for ac4C on mRNA not identified
    • selectivity mechanism for viral versus host RNA modification unclear
  9. 2024 Medium

    Key mechanistic gaps were addressed: NAT10's intrinsic RecD helicase domain was shown to directly unwind R-loops in parallel with DDX21 acetylation; PCBP1/2 and TDP43 were identified as adaptor proteins that recruit NAT10 to mRNA substrates; NAT10 phase separation via its IDR was linked to SRSF2 acetylation and alternative splicing; and lactylation by ATAT1 enhances NAT10 tRNA acetyltransferase activity for KSHV reactivation.

    Evidence In vitro helicase reconstitution with ΔRHD mutants; Co-IP and acRIP-seq after adaptor knockdown; phase separation assays with deletion mutants; lactylation assays with site mutagenesis

    PMID:38879723 PMID:39024555 PMID:39394182 PMID:39556689

    Open questions at the time
    • structural basis of adaptor-NAT10 interaction not resolved
    • whether phase separation is required for all NAT10 substrates or specific contexts unknown
    • lactylation site on NAT10 not precisely mapped in published data
  10. 2025 High

    In vivo conditional knockouts demonstrated tissue-specific ac4C-dependent translational programs: NAT10 enhances Myc mRNA translation for T cell expansion, reprograms serine metabolism via SLC1A4/HOXA9/MENIN translation in AML stem cells, and stabilizes CCL2/CXCL1 mRNAs to drive renal inflammation, establishing NAT10 as a central translational rheostat across immune and metabolic contexts.

    Evidence T cell CKO with ac4C-RIP and ribosome profiling during LCMV infection; AML CKO with translatomics and ribosome profiling; kidney CKO/CKI with ac4C-RIP-seq and chemokine neutralization

    PMID:39506072 PMID:40045031 PMID:40261924

    Open questions at the time
    • global catalog of tissue-specific ac4C target mRNAs incomplete
    • whether NAT10's protein acetylation and RNA acetylation activities are coupled in vivo unknown
    • no high-resolution structure of full-length human NAT10 with RNA substrate available

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions include the structural basis for NAT10's dual helicase-acetyltransferase mechanism on R-loops, the identity and specificity of ac4C reader proteins on mRNA, the full landscape of adaptor-dependent versus adaptor-independent RNA substrate selection, and how NAT10's protein and RNA acetyltransferase activities are partitioned and coordinated in different cellular compartments.
  • no crystal/cryo-EM structure of full-length human NAT10 with RNA
  • ac4C reader proteins on mRNA not identified
  • mechanism partitioning protein vs. RNA acetyltransferase outputs unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 20 GO:0140096 catalytic activity, acting on a protein 8 GO:0140098 catalytic activity, acting on RNA 7 GO:0003723 RNA binding 4 GO:0140657 ATP-dependent activity 1
Localization
GO:0005730 nucleolus 5 GO:0005634 nucleus 4 GO:0005654 nucleoplasm 2 GO:0005829 cytosol 1
Pathway
R-HSA-8953854 Metabolism of RNA 8 R-HSA-392499 Metabolism of proteins 5 R-HSA-73894 DNA Repair 5 R-HSA-1640170 Cell Cycle 3 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3 R-HSA-1430728 Metabolism 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-9612973 Autophagy 1
Partners
DDX21MORC2NPM1PARP1PCBP1SRSF2TDP43USP39

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 NAT10 acetyltransferase activity mediates nuclear shape rescue in laminopathic cells (lamin A/C-depleted and HGPS patient cells) via microtubule reorganization; chemical inhibition by Remodelin targets NAT10 to improve nuclear architecture and chromatin organization. Chemical-genetic approach: small molecule (Remodelin) identification, siRNA knockdown, cellular rescue assays, chemical and genetic validation Science High 24786082
2007 NAT10 (hALP) functions as a membrane-associated histone acetyltransferase that, together with the inner nuclear membrane protein hsSUN1, acetylates histones during mitotic chromosome de-condensation at the end of mitosis. Functional cellular assays, HAT activity assays, co-localization with hsSUN1 at inner nuclear membrane The Journal of biological chemistry Medium 17631499
2016 NAT10 acetylates p53 at lysine 120 (K120) and promotes Mdm2 degradation via an intrinsic E3 ligase activity; after DNA damage, NAT10 translocates from nucleolus to nucleoplasm to activate p53-mediated cell cycle control and apoptosis. In vitro acetylation assays, co-immunoprecipitation, E3 ligase assays, subcellular fractionation/immunofluorescence, siRNA knockdown with phenotypic readout EMBO reports High 26882543
2016 NAT10 autoacetylates itself at lysine 426 (K426); K426 acetylation is required for NAT10 to acetylate UBF, recruit PAF53 and RNA Polymerase I to rDNA, and activate pre-rRNA transcription. K426R mutant retains UBF binding but loses UBF acetylation and rRNA transcription activation. In vitro autoacetylation assay, site-directed mutagenesis (K426R), co-immunoprecipitation, rRNA transcription assays Biochemical and biophysical research communications High 27993683
2018 NAT10 inhibition normalizes HGPS phenotypes by rebalancing the nuclear-to-cytoplasmic ratio of Transportin-1 (TNPO1); microtubule stabilization in HGPS cells sequesters TNPO1 in the cytoplasm, disrupting nuclear pore integrity, RanGTP localization, and chromatin organization, all rescued by NAT10 inhibition. Subcellular fractionation, immunofluorescence, RNAi, pharmacological inhibition (Remodelin), nuclear import assays in HGPS patient fibroblasts and aged cells Science signaling High 29970603
2018 Under adequate energy supply, NAT10 is acetylated and promotes rRNA biogenesis while inhibiting autophagy by binding to and acetylating the autophagy regulator Che-1 at K228, suppressing Che-1-mediated transcription of Redd1 and Deptor. Upon energy stress, Sirt1 deacetylates NAT10, suppressing rRNA biogenesis and releasing autophagy inhibition. Co-immunoprecipitation, in vitro acetylation assays, Sirt1 deacetylation assays, autophagy and rRNA biogenesis functional assays, energy stress treatments Nucleic acids research High 30165671
2018 NAT10 nucleolar localization requires two nuclear/nucleolar localization signals (residues 68–75 and 989–1018); deletion of residues 989–1018 causes cytoplasmic/membrane translocation, where mislocalized NAT10 acetylates α-tubulin, stabilizes microtubules, and promotes hepatocellular carcinoma cell migration and invasion. GFP-deletion mutant imaging, immunofluorescence co-localization with α-tubulin and integrin, tubulin acetylation assays, migration/invasion assays Biochemical and biophysical research communications High 29634924
2017 NAT10 interacts with and stabilizes mutant p53 by counteracting Mdm2 in hepatocellular carcinoma cells, promoting HCC cell proliferation; confirmed by co-immunoprecipitation of NAT10 with mutant p53 and Mdm2. Co-immunoprecipitation, siRNA knockdown, Western blot, cell proliferation assay BMC cancer Medium 28859621
2022 PARP1 catalyzes PARylation of NAT10 at three conserved C-terminal lysine residues (K1016, K1017, K1020) within the nucleolar localization signal after DNA damage; this PARylation is required for NAT10 nucleoplasmic translocation and its function in acetylating MORC2 at K767 in DNA damage response. PARylation-deficient NAT10 (K3A) cannot relocalize and sensitizes cells to DNA damage agents. CRISPR-Cas9 KO, in vitro PARylation assay, site-directed mutagenesis (K3A), immunofluorescence, co-immunoprecipitation, clonogenic survival assay Cell communication and signaling High 35986334
2019 NAT10 and its yeast ortholog Kre33 are RNA acetyltransferases that catalyze N4-acetylcytidine (ac4C) modifications in 18S rRNA and participate in 40S ribosomal subunit assembly and pre-rRNA processing. Review synthesizing biochemical and structural data; underlying original studies include acetyltransferase assays and ribosome biogenesis assays Cells Medium 31491951
2022 NAT10-mediated ac4C modification of ULK1 mRNA stabilizes ULK1 transcripts and maintains ULK1 expression in neutrophils; loss of NAT10 reduces ULK1, enhancing STING-IRF3 signaling and NLRP3 inflammasome-driven pyroptosis in sepsis. ac4C-RIP, mRNA stability assay, overexpression/KD in vivo (neutrophil-specific), STING pathway activation readouts, mouse sepsis model Communications biology Medium 36068299
2022 LINC00623 lncRNA binds NAT10 and blocks its ubiquitination-dependent degradation by recruiting the deubiquitinase USP39, thereby stabilizing NAT10 protein and promoting its ac4C modification of oncogenic mRNAs in pancreatic cancer. RNA pulldown, RNA immunoprecipitation, co-immunoprecipitation, rescue experiments, in vitro and in vivo functional assays Journal of hematology & oncology Medium 35978332
2023 2-Hydroxyisobutyrylation (Khib) of NAT10 at lysine 823 enhances its interaction with deubiquitinase USP39, increasing NAT10 protein stability; stabilized NAT10 in turn promotes NOTCH3 mRNA stability via N4-acetylcytidine modification to drive cancer metastasis. Khib proteome profiling by MS, CRISPR/Cas9 functional screening, Co-IP, site-specific mutagenesis, in vivo tumor models Cell research High 36882514
2023 NAT10 stabilizes AHNAK mRNA via ac4C modification, protecting it from exonucleases; AHNAK-mediated DNA damage repair is required for NAT10-induced cisplatin resistance in bladder cancer. NFκB p65 directly binds the NAT10 promoter to activate NAT10 transcription upon cisplatin treatment. ac4C-RIP, mRNA stability assay, in vitro/in vivo cisplatin resistance models, ChIP assay, bladder cancer organoids, mouse xenografts Cancer research High 36939377
2023 NAT10 catalyzes ac4C modification of PAN lncRNA (encoded by KSHV), stabilizing PAN RNA and triggering KSHV lytic reactivation; mutagenesis of ac4C sites in PAN RNA abolishes ac4C modification, downregulates viral lytic genes, and reduces virion production. NAT10 also acetylates IFI16 mRNA to promote inflammasome activation. ac4C site mutagenesis in viral genome context, NAT10 KD, ac4C-RIP, virion production assay, inflammasome activation assay Nature communications High 37816771
2024 NAT10 is lactylated by α-tubulin acetyltransferase 1 (ATAT1) at a critical domain; this lactylation enhances NAT10 RNA acetyltransferase activity, increasing ac4C modification of tRNASer-CGA-1-1, which boosts translation efficiency of KSHV viral lytic genes and promotes KSHV reactivation. KSHV PAN RNA orchestrates NAT10 and ATAT1 to enhance NAT10 lactylation. Site-specific mutagenesis of tRNA ac4C sites, Co-IP of NAT10/ATAT1, lactylation assays, translation efficiency assay, virion production Cell death and differentiation Medium 38879723
2022 NAT10-mediated ac4C modification is required for male meiosis entry and progression in vivo; germ cell-specific Nat10 ablation in mice severely inhibits meiotic entry, causes defects in homologous chromosome synapsis, meiotic recombination, and repair of DNA double-strand breaks. Germ cell-specific conditional knockout (CKO) mouse model, transcriptomic profiling, cytological meiosis analyses Nucleic acids research High 35801907
2023 Maternal NAT10/ac4C modification controls oocyte meiotic cell-cycle progression by sculpting the maternal transcriptome through timely degradation of poly(A) tail mRNAs, achieved via ac4C deposition on CCR4-NOT complex transcripts. Oocyte-specific genetic knockout, poly(A) tail length assay (HA-PAT method devised), transcriptomic profiling, ac4C detection Nature communications High 37349316
2023 NAT10 promotes esophageal cancer (ESCA) progression via ac4C modification of tRNAs; depletion of NAT10 reduces ac4C-modified tRNA abundance and decreases translation efficiency of mRNAs enriched for ac4C-modified tRNA-decoded codons, with EGFR identified as a key downstream target. tRNA ac4C profiling, ribosome profiling, acRIP-seq, siRNA/shRNA KD, in vitro and in vivo tumor models, EGFR target validation Cell reports High 37463108
2024 NAT10 resolves nucleolar R-loops through two parallel pathways: (1) its intrinsic RecD helicase domain (RHD) directly unwinds R-loops; (2) its acetyltransferase activity acetylates DDX21 at K236 and K573, enhancing DDX21 helicase activity to further resolve R-loops. NAT10 depletion causes nucleolar R-loop accumulation and DNA damage. In vitro helicase assay, domain deletion mutants (ΔRHD), NAT10 acetyltransferase-dead mutant (G641E), Co-IP/GST pulldown, mass spectrometry of acetylation sites, DDX21 2KR/2KQ mutagenesis, CRISPR-Cas9 KO, γH2AX readout Cell communication and signaling High 39394182
2022 NAT10 and DDX21 interact with RNase H1 and enhance its endonuclease activity; purified NAT10 and DDX21 proteins increase RNase H1 cleavage rates in vitro, and reduction of either protein decreases PS-ASO activity and increases R-loop levels. BioID proximity labeling, biochemical confirmation, in vitro RNase H1 cleavage assay with purified proteins, R-loop quantification, PS-ASO activity assays Nucleic acid therapeutics High 35852833
2024 NAT10 undergoes liquid-liquid phase separation via a C-terminal intrinsically disordered region; this phase separation is essential for NAT10's tumor-promoting function. Phase-separated NAT10 interacts with and acetylates the splicing factor SRSF2, increasing SRSF2 stability; acetylated SRSF2 directly binds YTHDF1 pre-mRNA to promote exon 4 skipping and produce a short oncogenic YTHDF1 isoform. Phase separation assays, deletion mutants, Co-IP, acetylation assay of SRSF2, RIP for pre-mRNA binding, alternative splicing analysis, patient-derived organoids, in vivo models Cancer research Medium 39024555
2024 PCBP1/2 and TDP43 function as NAT10 adaptors for mRNA ac4C modification in mammalian cells; these RNA-binding proteins tether NAT10 to mRNA substrates and direct cytidine-rich ac4C motif selection. Knockdown of adaptors reduces mRNA acetylation abundance and ablates cytidine-rich ac4C motifs. Co-immunoprecipitation, acRIP-seq after adaptor knockdown, identification of sequence motif changes, mouse testis validation Advanced science Medium 39556689
2024 NAT10 facilitates NPM1 acetylation (identified by Co-IP and mass spectrometry), leading to enhanced NPM1-dependent transcription and increased PD-L1 expression; Remodelin inhibits NAT10, reduces NPM1 acetylation, and decreases PD-L1 expression. Co-immunoprecipitation, mass spectrometry, luciferase transcription assay, Remodelin treatment, in vivo anti-CTLA-4 combination model Molecular medicine Medium 38243170
2024 RNPS1 inhibits ZSWIM6-mediated ubiquitination degradation of NAT10 through direct protein-protein interaction, stabilizing NAT10 protein; elevated NAT10 then enhances tRNA ac4C modifications at novel sites (discovered by TRMC-seq), boosting translation of cancer-promoting mRNAs in HNSCC. Co-IP, ubiquitination assay, TRMC-seq (novel tRNA ac4C sequencing), translation assay, KD/OE functional studies International journal of oral science Medium 38246918
2022 HAAPIR piRNA directly interacts with NAT10 and enhances ac4C acetylation of Tfec mRNA, increasing TFEC expression, which transcriptionally upregulates pro-apoptotic BIK, promoting cardiomyocyte apoptosis after myocardial infarction. RNA immunoprecipitation (RIP), ac4C assay on Tfec mRNA, HAAPIR-deletion mouse model, cardiomyocyte apoptosis readout Advanced science Medium 35138696
2023 NAT10-mediated ac4C modification of MDM2 mRNA stabilizes MDM2 transcript, leading to MDM2 upregulation and p53 downregulation, facilitating gastric carcinogenesis; Helicobacter pylori infection induces NAT10 to activate this Hp-NAT10-MDM2-p53 axis. ac4C-RIP, mRNA stability assay, in vitro/in vivo gastric cancer models, Western blot for p53/MDM2 levels Journal of experimental & clinical cancer research Medium 36609449
2021 NAT10-mediated ac4C modification of RUNX2 mRNA stabilizes RUNX2 transcript and promotes its protein expression; NAT10 silencing decreases RUNX2 mRNA half-life and protein levels, impairing osteogenic differentiation of BMSCs. ac4C-RIP, mRNA half-life assay, NAT10 KD/OE in BMSCs, calcium nodule formation, OVX mouse model Molecular therapy. Nucleic acids Medium 34513300
2025 NAT10/ac4C modification drives leukaemogenesis and leukaemic stem cell self-renewal by reprogramming serine metabolism; mechanistically, NAT10 enhances ac4C-mediated translation of SLC1A4 (serine transporter), HOXA9, and MENIN, which activate serine synthesis pathway genes. Fludarabine inhibits NAT10 and targets this metabolic vulnerability. acRIP-seq, translatomics, ribosome profiling, conditional KO in AML models, in vitro/in vivo anti-leukemia assays, fludarabine as NAT10 inhibitor Nature cell biology High 39506072
2025 During T cell activation, NAT10 is upregulated and mediates ac4C modification of Myc mRNA, enhancing MYC protein translation efficiency to support rapid T cell expansion. Conditional deletion of Nat10 in T cells causes cell cycle arrest and impaired expansion due to MYC deficiency. Conditional Nat10 KO in T cells, ac4C-RIP of Myc mRNA, ribosome profiling/translation efficiency assay, LCMV infection model, T cell proliferation assays Nature immunology High 40045031
2022 NAT10 overexpression promotes PARP1 acetylation, increasing PARP1 half-life; acetylated PARP1 recruits DNA damage repair proteins XRCC1 and LIG3 to damage sites, enhancing DNA repair and platinum drug resistance in breast cancer cells. Co-immunoprecipitation, PARP1 acetylation assay, PARP1 half-life assay, XRCC1/LIG3 recruitment, γH2AX assay, apoptosis by flow cytometry Zhonghua zhong liu za zhi Medium 35754228
2023 NAT10-mediated ac4C modification of SYT9 (Syt9) mRNA stabilizes SYT9 protein in dorsal root ganglion neurons; upstream transcription factor USF1 binds the Nat10 promoter to increase NAT10 expression after peripheral nerve injury, driving neuropathic pain behaviors. Genetic deletion or KD of NAT10 in DRG abolishes Syt9 ac4C and SYT9 upregulation, providing antinociception. ChIP for USF1 at Nat10 promoter, acRIP of Syt9 mRNA, conditional NAT10 KO in DRG, nociceptive behavioral assays, Western blot The Journal of neuroscience High 36898834
2024 Cardiac-specific knockout of NAT10 reduces mRNA ac4C modification, suppresses translation efficiency of Kmt5a mRNA specifically (identified by ribosome footprinting + RNA-seq), reduces KMT5A protein, activates p53 signaling, induces cardiomyocyte apoptosis, and causes heart failure. Kmt5a KD recapitulates the phenotype; Kmt5a OE rescues NAT10 inhibition-induced apoptosis. Cardiac-specific CKO, ribosome footprint sequencing, RNA-seq, ac4C detection on Kmt5a mRNA, rescue experiments with Kmt5a OE Journal of the American Heart Association High 39392166
2024 NAT10-mediated ac4C modification of ITGB1 and Col1a2 mRNAs increases their stability; stabilized ITGB1 activates FAK downstream signaling to promote VSMC proliferation and vascular neointima formation after injury. acRIP-seq, RIP-seq, RNA-seq in VSMC, NAT10 VSMC-specific deletion, vascular injury mouse model, Remodelin treatment European heart journal Medium 39453784
2024 NAT10-mediated ac4C modification of ACOT7 mRNA enhances its stability and translation, modulating fatty acid metabolism and suppressing ferroptosis in ovarian cancer; IGF2BP1 enhances NAT10 mRNA translation in an m6A-dependent manner, placing NAT10 downstream of m6A signaling. acRIP-seq, mRNA stability assay, translation assay, ferroptosis assay, m6A-IGF2BP1 interaction for NAT10 translation, xenograft and organoid models Oncogene Medium 39390256
2024 NAT10/ac4C modification stabilizes ANP32B mRNA, modulating chromatin landscape (Wnt/TGFβ pathway regulators) during hESC lineage differentiation and pluripotent reprogramming; suppression of NAT10 affects lineage fate transitions. acRIP-seq, protein level changes of chromatin regulators, hESC differentiation/reprogramming assays, integrative multi-omics Science advances Medium 38215194
2024 NAT10 promotes osteoclastogenesis by catalyzing ac4C modification of Fos mRNA, stabilizing c-Fos, activating MAPK signaling, and AP-1 (c-Fos/c-Jun) transcription; NAT10 inhibition with Remodelin reduces alveolar bone loss in vivo. acRIP-qPCR, RIP-qPCR, mRNA decay assay, luciferase reporter, tartrate-resistant acid phosphatase staining, bone resorption pit assay, periodontitis mouse model Journal of advanced research Medium 39089619
2025 Nat10-mediated ac4C modification enhances translation efficiency of Nfatc1 mRNA in osteoclast precursors, promoting Nfatc1 expression and osteoclast maturation; monocyte-specific Nat10 KO alleviates OVX-induced bone loss. Epitranscriptomic and translatomic analyses, monocyte-specific CKO mouse, OVX bone loss model, Remodelin treatment Proceedings of the National Academy of Sciences Medium 40193598
2025 NAT10 promotes acute renal inflammation by enhancing ac4C modification of CCL2 and CXCL1 mRNAs, increasing their stability and promoting macrophage/neutrophil recruitment; conditional NAT10 KO in mouse kidneys attenuates renal dysfunction and inflammation, while conditional KI exacerbates it. ac4C-RIP-seq + RNA-seq in kidney, conditional CKO and CKI mouse models, chemokine neutralization, pharmacological inhibition (Cpd-155), AAV9-mediated silencing Proceedings of the National Academy of Sciences High 40261924

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Chemical inhibition of NAT10 corrects defects of laminopathic cells. Science (New York, N.Y.) 315 24786082
2023 NAT10 Drives Cisplatin Chemoresistance by Enhancing ac4C-Associated DNA Repair in Bladder Cancer. Cancer research 168 36939377
2016 NAT10 regulates p53 activation through acetylating p53 at K120 and ubiquitinating Mdm2. EMBO reports 161 26882543
2022 NAT10-mediated mRNA N4-acetylcytidine modification promotes bladder cancer progression. Clinical and translational medicine 146 35522942
2023 Lysine 2-hydroxyisobutyrylation of NAT10 promotes cancer metastasis in an ac4C-dependent manner. Cell research 132 36882514
2022 Acetyltransferase NAT10 regulates the Wnt/β-catenin signaling pathway to promote colorectal cancer progression via ac4C acetylation of KIF23 mRNA. Journal of experimental & clinical cancer research : CR 131 36522719
2023 Mechanisms of NAT10 as ac4C writer in diseases. Molecular therapy. Nucleic acids 116 37128278
2023 NAT10/ac4C/FOXP1 Promotes Malignant Progression and Facilitates Immunosuppression by Reprogramming Glycolytic Metabolism in Cervical Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 106 37818745
2023 N4-Acetylcytidine Drives Glycolysis Addiction in Gastric Cancer via NAT10/SEPT9/HIF-1α Positive Feedback Loop. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 104 37328448
2022 PIWI-Interacting RNA HAAPIR Regulates Cardiomyocyte Death After Myocardial Infarction by Promoting NAT10-Mediated ac4 C Acetylation of Tfec mRNA. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 99 35138696
2007 Histone acetyltransferase hALP and nuclear membrane protein hsSUN1 function in de-condensation of mitotic chromosomes. The Journal of biological chemistry 99 17631499
2023 Helicobacter pylori-induced NAT10 stabilizes MDM2 mRNA via RNA acetylation to facilitate gastric cancer progression. Journal of experimental & clinical cancer research : CR 91 36609449
2018 Deacetylation of NAT10 by Sirt1 promotes the transition from rRNA biogenesis to autophagy upon energy stress. Nucleic acids research 89 30165671
2021 ac4C acetylation of RUNX2 catalyzed by NAT10 spurs osteogenesis of BMSCs and prevents ovariectomy-induced bone loss. Molecular therapy. Nucleic acids 87 34513300
2022 NAT10 regulates neutrophil pyroptosis in sepsis via acetylating ULK1 RNA and activating STING pathway. Communications biology 81 36068299
2018 Inhibition of the acetyltransferase NAT10 normalizes progeric and aging cells by rebalancing the Transportin-1 nuclear import pathway. Science signaling 74 29970603
2017 NAT10 is upregulated in hepatocellular carcinoma and enhances mutant p53 activity. BMC cancer 72 28859621
2022 NAT10-mediated N4-acetylcytidine modification is required for meiosis entry and progression in male germ cells. Nucleic acids research 70 35801907
2023 NAT10-dependent N4-acetylcytidine modification mediates PAN RNA stability, KSHV reactivation, and IFI16-related inflammasome activation. Nature communications 66 37816771
2023 Role of NAT10-mediated ac4C-modified HSP90AA1 RNA acetylation in ER stress-mediated metastasis and lenvatinib resistance in hepatocellular carcinoma. Cell death discovery 64 36765042
2023 NAT10-mediated ac4C tRNA modification promotes EGFR mRNA translation and gefitinib resistance in cancer. Cell reports 64 37463108
2023 NAT10 Is Involved in Cardiac Remodeling Through ac4C-Mediated Transcriptomic Regulation. Circulation research 64 37955115
2023 Emerging roles of RNA ac4C modification and NAT10 in mammalian development and human diseases. Pharmacology & therapeutics 59 38065232
2022 The LINC00623/NAT10 signaling axis promotes pancreatic cancer progression by remodeling ac4C modification of mRNA. Journal of hematology & oncology 58 35978332
2023 Maternal NAT10 orchestrates oocyte meiotic cell-cycle progression and maturation in mice. Nature communications 57 37349316
2023 NAT10 regulates the LPS-induced inflammatory response via the NOX2-ROS-NF-κB pathway in macrophages. Biochimica et biophysica acta. Molecular cell research 53 37307924
2016 Autoacetylation of NAT10 is critical for its function in rRNA transcription activation. Biochemical and biophysical research communications 53 27993683
2018 Loss of nucleolar localization of NAT10 promotes cell migration and invasion in hepatocellular carcinoma. Biochemical and biophysical research communications 51 29634924
2019 miR-6716-5p promotes metastasis of colorectal cancer through downregulating NAT10 expression. Cancer management and research 48 31239781
2024 The positive feedback loop of the NAT10/Mybbp1a/p53 axis promotes cardiomyocyte ferroptosis to exacerbate cardiac I/R injury. Redox biology 47 38583415
2019 Recent Advances on the Structure and Function of RNA Acetyltransferase Kre33/NAT10. Cells 47 31491951
2021 Remodelin, a N-acetyltransferase 10 (NAT10) inhibitor, alters mitochondrial lipid metabolism in cancer cells. Journal of cellular biochemistry 46 34605570
2017 Inhibition of NAT10 Suppresses Melanogenesis and Melanoma Growth by Attenuating Microphthalmia-Associated Transcription Factor (MITF) Expression. International journal of molecular sciences 46 28880216
2024 Lactylation of NAT10 promotes N4-acetylcytidine modification on tRNASer-CGA-1-1 to boost oncogenic DNA virus KSHV reactivation. Cell death and differentiation 43 38879723
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
2021 The preoperative hemoglobin, albumin, lymphocyte and platelet (HALP) score is a useful predictor in patients with resectable esophageal squamous cell carcinoma. Bosnian journal of basic medical sciences 42 33974528
2024 N-acetyltransferase NAT10 controls cell fates via connecting mRNA cytidine acetylation to chromatin signaling. Science advances 38 38215194
2024 NAT10 Promotes Prostate Cancer Growth and Metastasis by Acetylating mRNAs of HMGA1 and KRT8. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 37 38922788
2023 N4-acetylcytidine-dependent GLMP mRNA stabilization by NAT10 promotes head and neck squamous cell carcinoma metastasis and remodels tumor microenvironment through MAPK/ERK signaling pathway. Cell death & disease 37 37914704
2024 NAT10/ac4C/JunB facilitates TNBC malignant progression and immunosuppression by driving glycolysis addiction. Journal of experimental & clinical cancer research : CR 35 39363363
2023 The emerging roles of ac4C acetylation "writer" NAT10 in tumorigenesis: A comprehensive review. International journal of biological macromolecules 31 37926318
2022 NAT10 acetylates BCL-XL mRNA to promote the proliferation of multiple myeloma cells through PI3K-AKT pathway. Frontiers in oncology 31 35978804
2024 The role and mechanism of NAT10-mediated ac4C modification in tumor development and progression. MedComm 30 39640362
2025 NAT10 promotes vascular remodelling via mRNA ac4C acetylation. European heart journal 29 39453784
2024 NAT10-mediated ac4C-modified ANKZF1 promotes tumor progression and lymphangiogenesis in clear-cell renal cell carcinoma by attenuating YWHAE-driven cytoplasmic retention of YAP1. Cancer communications (London, England) 29 38407929
2023 The Cytidine N-Acetyltransferase NAT10 Participates in Peripheral Nerve Injury-Induced Neuropathic Pain by Stabilizing SYT9 Expression in Primary Sensory Neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 28 36898834
2022 Poly(ADP-ribosyl)ation of acetyltransferase NAT10 by PARP1 is required for its nucleoplasmic translocation and function in response to DNA damage. Cell communication and signaling : CCS 28 35986334
2021 NAT10-Mediated N4-Acetylcytidine of RNA Contributes to Post-transcriptional Regulation of Mouse Oocyte Maturation in vitro. Frontiers in cell and developmental biology 28 34395433
2024 NAT10-mediated upregulation of GAS5 facilitates immune cell infiltration in non-small cell lung cancer via the MYBBP1A-p53/IRF1/type I interferon signaling axis. Cell death discovery 27 38762546
2018 CREB promotes laryngeal cancer cell migration via MYCT1/NAT10 axis. OncoTargets and therapy 27 29563811
2024 NAT10-mediated mRNA N4-acetylcytidine reprograms serine metabolism to drive leukaemogenesis and stemness in acute myeloid leukaemia. Nature cell biology 26 39506072
2023 NAT10 mediated mRNA acetylation modification patterns associated with colon cancer progression and microsatellite status. Epigenetics 26 36908042
2024 NAT10 Phase Separation Regulates YTHDF1 Splicing to Promote Gastric Cancer Progression. Cancer research 25 39024555
2024 m6A-driven NAT10 translation facilitates fatty acid metabolic rewiring to suppress ferroptosis and promote ovarian tumorigenesis through enhancing ACOT7 mRNA acetylation. Oncogene 23 39390256
2024 NAT10 promotes synovial aggression by increasing the stability and translation of N4-acetylated PTX3 mRNA in rheumatoid arthritis. Annals of the rheumatic diseases 22 38724075
2022 c-myc-mediated upregulation of NAT10 facilitates tumor development via cell cycle regulation in non-small cell lung cancer. Medical oncology (Northwood, London, England) 22 35834140
2023 Activated SIRT1 contributes to DPT-induced glioma cell parthanatos by upregulation of NOX2 and NAT10. Acta pharmacologica Sinica 21 37277492
2020 Remodelin, an inhibitor of NAT10, could suppress hypoxia-induced or constitutional expression of HIFs in cells. Molecular and cellular biochemistry 21 32529496
2024 Exosomal NAT10 from esophageal squamous cell carcinoma cells modulates macrophage lipid metabolism and polarization through ac4C modification of FASN. Translational oncology 20 38692194
2025 NAT10 Promotes Gastric Cancer Liver Metastasis by Modulation of M2 Macrophage Polarization and Metastatic Tumor Cell Hepatic Adhesion. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 19 39985269
2024 CLIC3 interacts with NAT10 to inhibit N4-acetylcytidine modification of p21 mRNA and promote bladder cancer progression. Cell death & disease 18 38182571
2023 Neutrophil extracellular traps promote gastric cancer cell metastasis via the NAT10-mediated N4-acetylcytidine modification of SMYD2. Cellular signalling 18 38110168
2024 Ropinirole suppresses LPS-induced periodontal inflammation by inhibiting the NAT10 in an ac4C-dependent manner. BMC oral health 17 38689229
2024 Targeting the NAT10/NPM1 axis abrogates PD-L1 expression and improves the response to immune checkpoint blockade therapy. Molecular medicine (Cambridge, Mass.) 16 38243170
2023 PARP-dependent and NAT10-independent acetylation of N4-cytidine in RNA appears in UV-damaged chromatin. Epigenetics & chromatin 16 37322549
2025 Acetyltransferase NAT10 inhibits T-cell immunity and promotes nasopharyngeal carcinoma progression through DDX5/HMGB1 axis. Journal for immunotherapy of cancer 15 39939141
2025 A critical role of N4-acetylation of cytidine in mRNA by NAT10 in T cell expansion and antiviral immunity. Nature immunology 15 40045031
2024 RNPS1 stabilizes NAT10 protein to facilitate translation in cancer via tRNA ac4C modification. International journal of oral science 15 38246918
2024 NAT10-mediated mRNA N4-acetylcytidine modification of MDR1 and BCRP promotes breast cancer progression. Thoracic cancer 15 38409918
2024 Remodelin delays non-small cell lung cancer progression by inhibiting NAT10 via the EMT pathway. Cancer medicine 13 38826095
2024 NAT10-mediated ac4C acetylation of TFRC promotes sepsis-induced pulmonary injury through regulating ferroptosis. Molecular medicine (Cambridge, Mass.) 13 39251905
2023 NAT10 promotes the tumorigenesis and progression of laryngeal squamous cell carcinoma through ac4C modification of FOXM1 mRNA. Cancer biology & therapy 12 37948132
2023 The mechanistic role of NAT10 in cancer: Unraveling the enigmatic web of oncogenic signaling. Pathology, research and practice 12 38056132
2024 NAT10 promotes osteoclastogenesis in inflammatory bone loss by catalyzing Fos mRNA ac4C modification and upregulating MAPK signaling pathway. Journal of advanced research 11 39089619
2024 Loss of NAT10 Reduces the Translation of Kmt5a mRNA Through ac4C Modification in Cardiomyocytes and Induces Heart Failure. Journal of the American Heart Association 11 39392166
2023 NAT10 Promotes Malignant Progression of Lung Cancer via the NF-κB Signaling Pathway. Discovery medicine 11 38058058
2023 Evaluation of the relationship between Hemoglobin, Albumin, Lymphocyte, Platelet (HALP) score and treatment modality and mortality in patients with ileus. Ulusal travma ve acil cerrahi dergisi = Turkish journal of trauma & emergency surgery : TJTES 11 38073459
2022 DARS-AS1 modulates cell proliferation and migration of gastric cancer cells by regulating miR-330-3p/NAT10 axis. Open medicine (Warsaw, Poland) 11 36568518
2025 NAT10 exacerbates acute renal inflammation by enhancing N4-acetylcytidine modification of the CCL2/CXCL1 axis. Proceedings of the National Academy of Sciences of the United States of America 10 40261924
2024 NAT10-mediated ac4C modification promotes stemness and chemoresistance of colon cancer by stabilizing NANOGP8. Heliyon 10 38726177
2024 NAT10 and cytidine acetylation in mRNA: intersecting paths in development and disease. Current opinion in genetics & development 10 38820741
2024 Establishing and Externally Validating a Hemoglobin, Albumin, Lymphocyte, and Platelet (HALP) Score-Based Nomogram for Predicting Early Recurrence in BCLC Stage 0/A Hepatocellular Carcinoma Patients After Radical Liver Resection: A Multi-Center Study. Journal of hepatocellular carcinoma 10 38895590
2025 Role of NAT10-mediated ac4C acetylation of ENO1 mRNA in glycolysis and apoptosis in non-small cell lung cancer cells. BMC pulmonary medicine 9 39948547
2025 Inhibition of tumor-intrinsic NAT10 enhances antitumor immunity by triggering type I interferon response via MYC/CDK2/DNMT1 pathway. Nature communications 9 40461504
2025 NAT10 regulates tumor progression and immune microenvironment in pancreatic ductal adenocarcinoma via the N4-acetylated LAMB3-mediated FAK/ERK pathway. Cancer communications (London, England) 9 40540648
2024 Could a reduced hemoglobin, albumin, lymphocyte, and platelet (HALP) score predict autoimmune hepatitis and degree of liver fibrosis? Revista da Associacao Medica Brasileira (1992) 9 38294124
2024 Dissecting the oncogenic properties of essential RNA-modifying enzymes: a focus on NAT10. Oncogene 9 38409550
2023 NAT10 regulates the repair of UVB-induced DNA damage and tumorigenicity. Toxicology and applied pharmacology 9 37716414
2025 Nat10-mediated N4-acetylcytidine modification enhances Nfatc1 translation to exacerbate osteoclastogenesis in postmenopausal osteoporosis. Proceedings of the National Academy of Sciences of the United States of America 8 40193598
2024 Decreased expression of NAT10 in peripheral blood mononuclear cells from new-onset ankylosing spondylitis and its clinical significance. Arthritis research & therapy 8 38167491
2024 NAT10 resolves harmful nucleolar R-loops depending on its helicase domain and acetylation of DDX21. Cell communication and signaling : CCS 8 39394182
2024 NAT10 promotes liver lipogenesis in mouse through N4-acetylcytidine modification of Srebf1 and Scap mRNA. Lipids in health and disease 8 39529018
2022 [Overexpression of NAT10 induced platinum drugs resistance in breast cancer cell]. Zhonghua zhong liu za zhi [Chinese journal of oncology] 8 35754228
2022 NAT10 and DDX21 Proteins Interact with RNase H1 and Affect the Performance of Phosphorothioate Oligonucleotides. Nucleic acid therapeutics 8 35852833
1996 Magnetochemical Properties and Reactions of Vanadium(III) Thiolate Complexes: Preparation of (NEt(4))(3)[V(3)Cl(6)(edt)(3)] and Mixed-Valence (NEt(4))[V(2)(edt)(4)] (edt = Ethane-1,2-dithiolate). Inorganic chemistry 8 11666852
2025 NAT10-mediated N4-acetylcytidine modification in KLF9 mRNA promotes adipogenesis. Cell death and differentiation 7 40123006
2025 Deciphering the role of acetylation-related gene NAT10 in colon cancer progression and immune evasion: implications for overcoming drug resistance. Discover oncology 7 40374962
2025 Targeting the NAT10/XIST/YAP1 Axis-Mediated Vascular Abnormalization Enhances Immune Checkpoint Blockade in Gastric Cancer. International journal of biological sciences 7 40860183
2024 PCBP1/2 and TDP43 Function as NAT10 Adaptors to Mediate mRNA ac4C Formation in Mammalian Cells. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 7 39556689
2024 Acetyltransferase NAT10 promotes an immunosuppressive microenvironment by modulating CD8+ T cell activity in prostate cancer. Molecular biomedicine 7 39648231