Affinage

NAT10

RNA cytidine acetyltransferase · UniProt Q9H0A0

Length
1025 aa
Mass
115.7 kDa
Annotated
2026-06-10
100 papers in source corpus 33 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NAT10 is a nucleolar bifunctional enzyme that couples N4-acetylcytidine (ac4C) deposition on RNA to protein lysine acetylation, acting as a central hub in ribosome biogenesis, mitosis, the DNA damage response, and gene-expression control across diverse physiological and disease contexts (PMID:31491951, PMID:39394182, PMID:40045031). Its core RNA function is to write ac4C on tRNAs, rRNA, mRNAs, and lncRNAs, thereby stabilizing transcripts and enhancing their translation efficiency; substrate selection is directed by RNA-binding adaptors PCBP1/2 and TDP43 that tether the enzyme to cytidine-rich motifs (PMID:39556689), and these activities tune the translation of specific targets including EGFR, MYC, and structural/metabolic regulators (PMID:37463108, PMID:40045031). NAT10 also functions as a protein acetyltransferase: it acetylates p53 at K120 and degrades Mdm2 through an intrinsic E3 ligase activity to stabilize p53 (PMID:26882543), acetylates the kinesin Eg5 at K771 to drive bipolar spindle assembly (PMID:35210604), acetylates DDX21 at K236/K573 and uses its own RecD helicase domain to resolve nucleolar R-loops (PMID:39394182), and acetylates SRSF2 within liquid-liquid phase-separated condensates to redirect splicing (PMID:39024555). NAT10 localizes predominantly to the nucleolus via two nucleolar localization signals and concentrates at the mitotic midbody, with depletion causing nucleolar assembly defects, cytokinesis failure, and G2/M arrest (PMID:19303003, PMID:29634924). Its nucleoplasmic relocation upon DNA damage is governed by PARP1-mediated PARylation at K1016/K1017/K1020, enabling MORC2 acetylation and recruitment to DNA:RNA hybrids that promote homologous recombination repair (PMID:35986334, PMID:40132530). NAT10 protein stability and activity are further modulated by 2-hydroxyisobutyrylation at K823 and lactylation that enhance its acetyltransferase output and protect it from ubiquitin-dependent degradation (PMID:38879723, PMID:36882514). Through these activities NAT10 governs oocyte maturation, cardiac physiology, adipogenesis, immune responses, and tumor progression (PMID:37349316, PMID:39392166, PMID:40261924, PMID:40045031).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 2009 High

    Established where NAT10 acts and that it is required for cell division, defining its nucleolar and mitotic localization and linking it to microtubule acetylation.

    Evidence Subcellular fractionation, GFP-fusion imaging, domain deletion, and siRNA knockdown in human cells

    PMID:19303003

    Open questions at the time
    • Direct enzymatic substrate at the midbody not defined
    • Mechanism linking NAT10 to tubulin acetylation unresolved
  2. 2014 High

    Showed NAT10 acetyltransferase activity is a druggable node for nuclear architecture, providing the chemical tool Remodelin and a therapeutic rationale in laminopathies.

    Evidence Chemical genetics with Remodelin plus siRNA and genetic rescue in lamin-depleted and HGPS patient cells

    PMID:24786082

    Open questions at the time
    • Molecular target of acetylation driving nuclear shape rescue not pinpointed
    • Microtubule reorganization mechanism partial
  3. 2016 High

    Defined NAT10 as a protein acetyltransferase with E3 ligase activity that stabilizes p53, expanding its role beyond RNA to the DNA damage/cell cycle axis.

    Evidence In vitro acetylation and ubiquitination assays, mutagenesis, and immunofluorescence showing nucleolar-to-nucleoplasmic translocation after DNA damage

    PMID:26882543

    Open questions at the time
    • Trigger and machinery for translocation not yet identified
    • Generality of E3 ligase activity unclear
  4. 2017 Medium

    Extended the p53 axis to oncogenic mutant p53, indicating context-dependent pro-tumor outcomes of NAT10 stabilization.

    Evidence Co-IP, knockdown, and growth assays in HCC cells

    PMID:28859621

    Open questions at the time
    • No in vitro reconstitution
    • Acetylation site on mutant p53 not mapped
  5. 2019 Medium

    Consolidated NAT10/Kre33 as the conserved enzyme for 18S rRNA acetylation and 40S subunit assembly, defining its core ribosome biogenesis role.

    Evidence Review synthesizing structural and functional rRNA processing/acetylation studies in yeast and human

    PMID:31491951

    Open questions at the time
    • Secondary source, not primary data
    • Quantitative contribution to human ribosome biogenesis not detailed here
  6. 2022 High

    Resolved how DNA-damage-induced relocation is controlled, showing PARP1 PARylation of the C-terminal NoLS drives nucleoplasmic translocation and MORC2 acetylation.

    Evidence In vitro PARylation assay, K3A mutagenesis, CRISPR KO, co-IP, and clonogenic survival

    PMID:35986334

    Open questions at the time
    • Full set of nucleoplasmic substrates incomplete
    • Reader of PARylated NAT10 not defined
  7. 2022 High

    Identified a mitotic protein substrate, showing Eg5 K771 acetylation stabilizes the motor and is required for bipolar spindle assembly.

    Evidence Co-IP, in vitro acetyltransferase assay, site-specific antibody, mutant rescue, and live imaging

    PMID:35210604

    Open questions at the time
    • Deacetylase counteracting K771 not identified
    • Temporal regulation across mitosis unclear
  8. 2022 Medium

    Linked NAT10 to R-loop and rRNA homeostasis through cooperation with DDX21 and RNase H1.

    Evidence BioID, co-IP, in vitro RNase H1 cleavage assay, and knockdown

    PMID:35852833

    Open questions at the time
    • Whether stimulation of RNase H1 requires catalytic NAT10 not separated
    • Single lab
  9. 2022 Medium

    Demonstrated ac4C as a physiologic mRNA-stabilizing mark with tissue phenotypes, in cardiomyocyte apoptosis (HAAPIR/Tfec) and neutrophil pyroptosis (ULK1).

    Evidence RIP/acRIP, RNA decay assays, and genetic mouse models (HAAPIR deletion; neutrophil-specific NAT10)

    PMID:35138696 PMID:36068299

    Open questions at the time
    • Adaptor specifying these mRNA targets not defined
    • Direct vs indirect effects not fully separated
  10. 2023 High

    Established PTM-driven control of NAT10 stability and activity via Khib at K823 (USP39 recruitment) feeding into ac4C-dependent NOTCH3 stabilization and metastasis.

    Evidence Khib proteome profiling, CRISPR screening, co-IP, mutagenesis, and mRNA stability assays

    PMID:36882514

    Open questions at the time
    • Khib writer/eraser dynamics on NAT10 not fully mapped
    • Breadth of downstream ac4C targets unclear
  11. 2023 Medium

    Showed NAT10 reprograms translation via tRNA ac4C, decreasing tRNA abundance and codon-biased translation when depleted, with EGFR as a key output.

    Evidence Ribosome profiling, tRNA ac4C profiling, and NAT10 depletion in ESCA models

    PMID:37463108

    Open questions at the time
    • Mechanism linking ac4C to tRNA abundance unresolved
    • Codon-decoding model not directly proven
  12. 2023 High

    Defined a maternal developmental requirement, with NAT10 ac4C on CCR4-NOT transcripts shaping the maternal transcriptome for oocyte maturation.

    Evidence Genetic knockout, poly(A) tail assays, transcriptomics, and ac4C-seq

    PMID:37349316

    Open questions at the time
    • How ac4C couples to deadenylation machinery mechanistically unclear
  13. 2023 High

    Extended ac4C to viral and immune RNAs, stabilizing KSHV PAN lncRNA and IFI16 mRNA to drive lytic reactivation and inflammasome activation.

    Evidence ac4C-seq, site mutagenesis in viral genome, knockdown, and RNA stability/virion assays

    PMID:37816771

    Open questions at the time
    • Selectivity for viral vs host transcripts not fully defined
  14. 2023 Medium

    Connected NAT10 to therapy resistance, stabilizing AHNAK mRNA for DNA repair and driving cisplatin resistance under NF-κB transcriptional control.

    Evidence acRIP-seq, RNA stability, ChIP, and in vitro/in vivo cisplatin assays

    PMID:36939377

    Open questions at the time
    • Single lab
    • Direct ac4C site contribution to AHNAK stability not mutationally proven
  15. 2023 Medium

    Clarified that ac4C RNA, not NAT10 itself, is recruited to DNA lesions in a PARP-dependent manner, refining the model of NAT10's role at damage sites.

    Evidence UV microirradiation, immunofluorescence with PARP inhibition, and NAT10 depletion (negative result)

    PMID:37322549

    Open questions at the time
    • Where ac4C marking of damage-associated RNA occurs is unresolved
    • Apparent tension with later DSB-recruitment findings
  16. 2024 Medium

    Showed NAT10 acts within phase-separated condensates to acetylate SRSF2 and reprogram splicing (YTHDF1), revealing a condensate-based mode of action.

    Evidence Phase separation assays, co-IP, in vitro acetylation, domain deletion, and patient organoids

    PMID:39024555

    Open questions at the time
    • IDR requirement for catalytic output not fully dissected
    • Single lab
  17. 2024 High

    Resolved dual mechanisms of R-loop resolution: direct RecD helicase unwinding plus DDX21 K236/K573 acetylation that boosts DDX21 helicase activity.

    Evidence In vitro helicase assay, GST pull-down, MS, CRISPR KO, RNase H-controlled imaging, and 2KR/2KQ mutagenesis

    PMID:39394182

    Open questions at the time
    • Relative contribution of helicase vs acetylase arms not quantified
  18. 2024 Medium

    Identified the adaptor logic of mRNA substrate selection, showing PCBP1/2 and TDP43 tether NAT10 and define ac4C site motifs.

    Evidence Co-IP, knockdown, acRIP-seq, and mass spectrometry

    PMID:39556689

    Open questions at the time
    • Hierarchy among adaptors not established
    • Single lab
  19. 2024 Medium

    Demonstrated lactylation by ATAT1 as an activating PTM that increases NAT10 RNA acetyltransferase output and tRNA ac4C to promote viral translation.

    Evidence Mass spectrometry, mutagenesis, tRNA ac4C and translation efficiency assays

    PMID:38879723

    Open questions at the time
    • Lactylation site stoichiometry and reversibility unclear
    • Single lab
  20. 2024 Medium

    Identified additional ubiquitination-stability regulators (LINC00623/USP39; RNPS1 vs ZSWIM6) and a new protein substrate NPM1 controlling PD-L1, broadening NAT10's regulatory and immune roles.

    Evidence RNA pulldown, co-IP, ubiquitination assays, MS, and functional readouts

    PMID:35978332 PMID:38243170 PMID:38246918

    Open questions at the time
    • NPM1 acetylation site not mapped
    • Interplay among competing E3/DUB regulators unclear
  21. 2024 High

    Established broad physiologic ac4C-target programs: adipogenesis (KLF9), hepatic lipogenesis (Srebf1/Scap), cardiac homeostasis (Kmt5a, Mybbp1a), and fibrosis (TGFβ1 via PTBP1).

    Evidence acRIP-seq/RIP, ribosome profiling, conditional/cardiac KO and AAV knockdown, and rescue experiments

    PMID:38583415 PMID:39392166 PMID:39529018 PMID:40123006 PMID:40817062

    Open questions at the time
    • Tissue-specific adaptor determinants not defined
    • Overlapping vs distinct target sets across tissues unclear
  22. 2025 High

    Provided structural and chromatin-level mechanism at DSBs, showing PARP1-dependent NAT10 accumulation and ac4C on DNA:RNA hybrids promotes homologous recombination, with a 2.9 Å cryo-EM NAT10–remodelin structure.

    Evidence Laser micro-irradiation, ChIP, cryo-EM, hepatocyte-specific KO, and xenograft/PDX models

    PMID:40132530

    Open questions at the time
    • Reconciliation with prior report that NAT10 does not accumulate at lesions needed
    • Hybrid-stabilizing mechanism at atomic detail incomplete
  23. 2025 High

    Defined immune-cell and inflammatory roles, with MYC mRNA ac4C enabling T cell expansion and CCL2/CXCL1 ac4C driving renal inflammation.

    Evidence Conditional/T-cell-specific KO and KI, ribosome profiling, acRIP-seq, neutralizing antibodies, and infection/AKI models

    PMID:40045031 PMID:40261924

    Open questions at the time
    • Signals upregulating NAT10 during activation not fully defined
    • Cell-type-specific target selection mechanism unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How NAT10 integrates its competing RNA-acetylase, protein-acetylase, E3-ligase, and helicase activities into context-specific outputs, and how PTMs and adaptors jointly select substrates in vivo, remains unresolved.
  • No unified model coordinating ac4C vs protein acetylation
  • Deacetylases/erasers for most NAT10 protein substrates unidentified
  • Quantitative rules governing adaptor-directed ac4C site choice unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0140098 catalytic activity, acting on RNA 5 GO:0016740 transferase activity 4 GO:0003723 RNA binding 3 GO:0016787 hydrolase activity 1 GO:0016874 ligase activity 1
Localization
GO:0005730 nucleolus 4 GO:0005634 nucleus 2 GO:0005654 nucleoplasm 2 GO:0005829 cytosol 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-8953854 Metabolism of RNA 4 R-HSA-1640170 Cell Cycle 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-73894 DNA Repair 3 R-HSA-74160 Gene expression (Transcription) 2
Partners
DDX21MORC2PARP1PCBP1PTBP1SRSF2TDP43USP39

Evidence

Reading pass · 33 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 via microtubule reorganization; chemical inhibition of NAT10 with Remodelin improves nuclear architecture in lamin A/C-depleted and HGPS patient cells. Chemical genetics (Remodelin), siRNA knockdown, genetic rescue, cellular morphology assays Science High 24786082
2009 NAT10 localizes predominantly to the nucleolus in interphase and concentrates in the mitotic midbody during telophase; the N-terminal domain (residues 549–834) mediates this localization. NAT10 depletion causes defects in nucleolar assembly, cytokinesis, decreased acetylated α-tubulin, and G2/M cell cycle arrest, indicating a role in microtubule acetylation and cell division. Subcellular fractionation, GFP-fusion live imaging, domain deletion mutants, siRNA knockdown, flow cytometry Experimental cell research High 19303003
2016 NAT10 acetylates p53 at K120 and promotes Mdm2 degradation via its intrinsic E3 ligase activity, thereby stabilizing p53 and activating p53-mediated cell cycle control and apoptosis. After DNA damage, NAT10 translocates from the nucleolus to the nucleoplasm. Immunoprecipitation, in vitro acetylation assay, ubiquitination assay, siRNA knockdown, site-directed mutagenesis, immunofluorescence EMBO reports High 26882543
2022 NAT10 acetylates the kinesin motor protein Eg5 at K771, stabilizing Eg5 and promoting its centrosome loading. NAT10 depletion causes monopolar and asymmetrical spindle formation, chromosome misalignment and mitotic catastrophe; K771 acetylation is required for Eg5 motor function. Co-immunoprecipitation, in vitro acetyltransferase assay, K771-Ac specific antibody, live-cell imaging, rescue with acetylation-mimetic mutant (K771Q), CRISPR/siRNA knockdown Cell death and differentiation High 35210604
2018 NAT10 nuclear localization is mediated by two nucleolar localization signals (NuLS) at residues 68–75 and 989–1018. A deletion mutant lacking residues 989–1018 translocates to cytoplasm; cytoplasmic/membranous NAT10 co-localizes with α-tubulin and promotes α-tubulin acetylation and microtubule stabilization, enhancing HCC cell migration and invasion. GFP-NAT10 deletion constructs, live imaging, immunofluorescence, migration/invasion assays Biochemical and biophysical research communications Medium 29634924
2019 NAT10/Kre33 participates in acetylation and processing of 18S rRNA and assembly of the 40S ribosomal subunit in yeast and humans, representing its core function in ribosome biogenesis. Review synthesizing structural and functional studies on Kre33/NAT10 including acetylation assays and rRNA processing experiments Cells Medium 31491951
2022 PARP1 PARylates NAT10 on three conserved lysine residues (K1016, K1017, K1020) within its C-terminal nucleolar localization signal after DNA damage. This PARylation is required for NAT10 translocation from nucleolus to nucleoplasm. PARylated NAT10 then co-localizes and interacts with MORC2 and acetylates MORC2 at K767, contributing to the DNA damage response. CRISPR-Cas9 KO, in vitro PARylation assay, mutagenesis (K3A mutant), immunofluorescence, co-IP, clonogenic survival assay Cell communication and signaling High 35986334
2017 NAT10 interacts with mutant p53 and counteracts Mdm2 action to increase mutant p53 protein levels in HCC cells, promoting proliferation. Immunoprecipitation, western blot, RNA interference, cell growth assay BMC cancer Medium 28859621
2023 NAT10 catalyzes ac4C modification on KSHV PAN lncRNA, stabilizing it and triggering viral lytic reactivation. NAT10 also acetylates IFI16 mRNA, enhancing its stability and translation, leading to inflammasome activation. Mutagenesis of ac4C sites in PAN RNA abolishes these effects. ac4C sequencing, mutagenesis of ac4C sites in KSHV genome, NAT10 knockdown, virion production assay, RNA stability assay Nature communications High 37816771
2024 NAT10 is lactylated by α-tubulin acetyltransferase 1 (ATAT1) at a critical domain, enhancing NAT10 RNA acetyltransferase activity and increasing ac4C modification of tRNASer-CGA-1-1, which boosts translation efficiency of KSHV viral lytic genes and promotes viral reactivation. Mass spectrometry, mutagenesis, tRNA ac4C modification assays, virion production assay, KSHV lytic gene translation efficiency measurement Cell death and differentiation Medium 38879723
2023 Lysine 2-hydroxyisobutyrylation (Khib) at K823 of NAT10 enhances its interaction with deubiquitinase USP39, increasing NAT10 protein stability. NAT10 in turn promotes metastasis by stabilizing NOTCH3 mRNA in an ac4C-dependent manner. Systemic Khib proteome profiling, CRISPR/Cas9 functional screening, Co-IP, mutagenesis, mRNA stability assay, acRIP Cell research High 36882514
2023 NAT10 binds and stabilizes AHNAK mRNA via ac4C modification to protect it from exonuclease-mediated decay, and AHNAK-mediated DNA damage repair is required for NAT10-induced cisplatin resistance in bladder cancer. NFκB p65 directly binds the NAT10 promoter to activate its transcription upon cisplatin treatment. acRIP-seq, RNA stability assay, ChIP, knockdown/overexpression with in vitro and in vivo cisplatin resistance assays Cancer research Medium 36939377
2023 NAT10-mediated ac4C modification of tRNAs reduces their abundance when NAT10 is depleted, decreasing translation efficiency of mRNAs enriched for ac4C-modified tRNA-decoded codons; EGFR is identified as a key downstream target regulated at the translational level through this tRNA ac4C mechanism. Ribosome profiling, tRNA ac4C profiling, NAT10 depletion, ESCA cell lines and mouse models Cell reports Medium 37463108
2023 Maternal NAT10/Nat10 is essential for oocyte meiotic prophase I progression and oocyte maturation by sculpting the maternal transcriptome through ac4C deposition on CCR4-NOT complex transcripts, enabling timely degradation of poly(A)-tailed mRNAs. Genetic knockout, poly(A) tail length assay (HA-PAT), transcriptomics, ac4C-seq Nature communications High 37349316
2024 NAT10 forms liquid-liquid phase separation condensates via a C-terminal intrinsically disordered region; within these condensates NAT10 interacts with splicing factor SRSF2, acetylates SRSF2 to increase its stability, and acetylated SRSF2 promotes YTHDF1 exon 4 skipping, producing a short tumor-promoting YTHDF1 transcript. Phase separation assays, Co-IP, in vitro acetylation, domain deletion, RNA splicing analysis, patient organoids Cancer research Medium 39024555
2024 PCBP1/2 and TDP43 function as RNA-binding protein adaptors that tether NAT10 to mRNA substrates and determine ac4C site selection; knockdown of these adaptors reduces mRNA acetylation abundance and ablates cytidine-rich ac4C motifs. Co-IP, knockdown, acRIP-seq, mass spectrometry Advanced science Medium 39556689
2024 NAT10 resolves nucleolar R-loops through two parallel mechanisms: (1) its RecD helicase domain (RHD) directly unwinds R-loops in vitro and in cells; (2) its acetyltransferase activity acetylates DDX21 at K236 and K573, enhancing DDX21 helicase activity to unwind nucleolar R-loops. NAT10 depletion causes nucleolar R-loop accumulation and DNA damage. In vitro helicase assay, Co-IP, GST pull-down, mass spectrometry, CRISPR-Cas9 KO, immunofluorescence with RNase H treatment, domain deletion mutants Cell communication and signaling High 39394182
2022 NAT10 and DDX21 physically interact with RNase H1 and enhance its endoribonuclease cleavage rate in vitro. Reduction of NAT10 and DDX21 decreases PS-ASO activity, impairs pre-rRNA processing, and increases R-loop levels in cells. BioID proximity labeling, biochemical Co-IP, in vitro RNase H1 cleavage assay, knockdown Nucleic acid therapeutics Medium 35852833
2025 NAT10 accumulates at DNA double-strand break (DSB) sites and executes ac4C modification on RNAs at DNA:RNA hybrids in a PARP1-dependent manner, enhancing the stability of DNA:RNA hybrids and promoting homologous recombination repair. Cryo-EM structure of NAT10–remodelin complex was determined at 2.9 Å, revealing a C2 symmetric architecture. Laser micro-irradiation, ChIP, cryo-EM structure determination, hepatocyte-specific KO mouse, xenograft and PDX tumor models Drug resistance updates High 40132530
2023 ac4C RNA accumulates at DNA lesions in UV-microirradiated cells within 2–45 min; however, NAT10 does not itself accumulate at damaged sites and NAT10 depletion does not affect ac4C recruitment to DNA lesions. The recruitment of ac4C RNA to damaged chromatin is PARP-dependent (blocked by olaparib). UV microirradiation, immunofluorescence, PARP inhibitor treatment, NAT10 depletion Epigenetics & chromatin Medium 37322549
2022 NAT10-mediated ac4C modification stabilizes HAAPIR piRNA-targeted Tfec mRNA, increasing TFEC expression which transcriptionally activates the pro-apoptotic gene BIK, promoting cardiomyocyte apoptosis during ischemia/reperfusion. HAAPIR piRNA directly interacts with NAT10 to enhance this ac4C acetylation. RNA immunoprecipitation, ac4C assays, HAAPIR deletion mouse model, ischemia/reperfusion model, apoptosis assay Advanced science Medium 35138696
2022 NAT10 depletion in neutrophils causes decay of ULK1 mRNA (an ac4C target) and reduced ULK1 expression, leading to enhanced STING-IRF3 signaling and NLRP3 inflammasome activation, driving neutrophil pyroptosis in sepsis. Neutrophil-specific NAT10 overexpression mouse model, acRIP, RNA decay assay, STING pathway analysis Communications biology Medium 36068299
2024 NAT10 promotes adipogenesis by mediating ac4C modification of KLF9 mRNA to enhance its stability, which activates the CEBPA/B-PPARG pathway; AAV-mediated NAT10 knockdown in adipose tissue inhibits adipose expansion in high-fat diet mice. acRIP-seq, RNA-seq, acRIP-PCR, dual-luciferase assay, AAV knockdown in vivo, Remodelin treatment Cell death and differentiation Medium 40123006
2024 NAT10 promotes liver lipogenesis by mediating ac4C modification of Srebf1 and Scap mRNAs, stabilizing them and activating lipogenic gene transcription; AAV-mediated NAT10 knockdown in mouse liver reduces lipogenesis. acRIP-PCR, NAT10-RIP-PCR, AAV knockdown, dot blot, Oil Red O staining, Remodelin treatment Lipids in health and disease Medium 39529018
2024 NAT10 facilitates acetylation of NPM1, which enhances NPM1-dependent transcription of PD-L1; Remodelin reduces NPM1 acetylation and decreases PD-L1 expression. NAT10 was identified as the NPM1 acetyltransferase by Co-IP and mass spectrometry. Co-immunoprecipitation, mass spectrometry, knockdown/inhibitor assays, PD-L1 expression measurement Molecular medicine Medium 38243170
2024 NAT10 mediates ac4C modification of Kmt5a (SET domain-containing protein 5a) mRNA to enhance its translation efficiency; cardiac-specific NAT10 KO reduces Kmt5a protein without changing its mRNA, activates p53 signaling, and causes cardiomyocyte apoptosis and heart failure. Kmt5a knockdown recapitulates the NAT10-null phenotype and Kmt5a overexpression rescues it. Cardiac-specific KO, ribosome footprint sequencing combined with RNA-seq, Kmt5a rescue by overexpression Journal of the American Heart Association High 39392166
2024 NAT10 promotes cardiomyocyte ferroptosis during I/R injury by mediating ac4C modification of Mybbp1a mRNA, increasing MYBBP1A stability, which activates p53 and represses SLC7A11 transcription. P53 in turn transcriptionally activates NAT10, forming a positive feedback loop. Cardiac-specific NAT10 KO/overexpression, acRIP, mRNA stability assay, Mybbp1a knockdown rescue, ferroptosis inhibitor Fer-1 Redox biology Medium 38583415
2025 NAT10 enhances ac4C modification of CCL2 and CXCL1 mRNAs to stabilize them, promoting macrophage and neutrophil recruitment and accelerating renal inflammation in acute kidney injury; conditional NAT10 KO attenuates and conditional KI exacerbates renal inflammation. Conditional KO/KI mouse models, ac4C-RIP-seq, RNA-seq, CCL2/CXCL1 neutralizing antibodies, AAV9 silencing, pharmacological inhibition PNAS High 40261924
2025 NAT10 ac4C-modifies GAS5 lncRNA to regulate its stability in NSCLC; GAS5 in turn stabilizes p53 by binding MYBBP1A and facilitating MYBBP1A-p53 interaction, enhancing p53-mediated IRF1 transcription and type I interferon signaling. RNA-binding assay, Co-IP, NAT10 acRIP, overexpression/knockdown functional assays Cell death discovery Medium 38762546
2025 During T cell activation, NAT10 is upregulated and its ac4C modification of Myc mRNA increases MYC protein translation efficiency, enabling rapid T cell expansion; conditional deletion of Nat10 in T cells causes cell cycle arrest and impaired expansion in an LCMV infection model. Conditional T-cell-specific Nat10 KO, ribosome profiling, translation efficiency assay, LCMV infection model Nature immunology High 40045031
2024 NAT10 mediates ac4C modification of TGFβ1 mRNA by physically interacting with RNA-binding protein PTBP1, enhancing TGFβ1 mRNA stability and promoting TGFβ/SMAD signaling-driven liver fibrosis and cellular senescence. acRIP-seq, RNA immunoprecipitation, NAT10 overexpression/KO in hepatic stellate cells, CCl4 mouse model, Remodelin treatment Genome medicine Medium 40817062
2024 LINC00623 binds NAT10 and recruits deubiquitinase USP39 to block ubiquitination-dependent NAT10 degradation, stabilizing NAT10 protein and thereby sustaining oncogenic mRNA ac4C modification in pancreatic cancer. RNA pulldown, RNA immunoprecipitation, Co-IP, ubiquitination assay, rescue experiments Journal of hematology & oncology Medium 35978332
2024 RNPS1 inhibits ubiquitination-mediated NAT10 degradation by E3 ligase ZSWIM6 through direct protein–protein interaction, maintaining NAT10 protein levels and tRNA ac4C modifications that support translation of oncogenic gene sets in HNSCC. Co-IP, ubiquitination assay, TRMC-seq (novel tRNA ac4C sequencing), translation efficiency measurement International journal of oral science Medium 38246918

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.) 321 24786082
2023 NAT10 Drives Cisplatin Chemoresistance by Enhancing ac4C-Associated DNA Repair in Bladder Cancer. Cancer research 174 36939377
2016 NAT10 regulates p53 activation through acetylating p53 at K120 and ubiquitinating Mdm2. EMBO reports 168 26882543
2022 NAT10-mediated mRNA N4-acetylcytidine modification promotes bladder cancer progression. Clinical and translational medicine 149 35522942
2009 NAT10, a nucleolar protein, localizes to the midbody and regulates cytokinesis and acetylation of microtubules. Experimental cell research 140 19303003
2023 Lysine 2-hydroxyisobutyrylation of NAT10 promotes cancer metastasis in an ac4C-dependent manner. Cell research 139 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 134 36522719
2023 Mechanisms of NAT10 as ac4C writer in diseases. Molecular therapy. Nucleic acids 124 37128278
2023 NAT10/ac4C/FOXP1 Promotes Malignant Progression and Facilitates Immunosuppression by Reprogramming Glycolytic Metabolism in Cervical Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 121 37818745
2023 N4-Acetylcytidine Drives Glycolysis Addiction in Gastric Cancer via NAT10/SEPT9/HIF-1α Positive Feedback Loop. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 111 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) 103 35138696
2023 Helicobacter pylori-induced NAT10 stabilizes MDM2 mRNA via RNA acetylation to facilitate gastric cancer progression. Journal of experimental & clinical cancer research : CR 95 36609449
2022 NAT10 promotes cell proliferation by acetylating CEP170 mRNA to enhance translation efficiency in multiple myeloma. Acta pharmaceutica Sinica. B 90 35967285
2022 NAT10 regulates neutrophil pyroptosis in sepsis via acetylating ULK1 RNA and activating STING pathway. Communications biology 82 36068299
2017 NAT10 is upregulated in hepatocellular carcinoma and enhances mutant p53 activity. BMC cancer 74 28859621
2023 NAT10-mediated ac4C tRNA modification promotes EGFR mRNA translation and gefitinib resistance in cancer. Cell reports 68 37463108
2023 NAT10-dependent N4-acetylcytidine modification mediates PAN RNA stability, KSHV reactivation, and IFI16-related inflammasome activation. Nature communications 68 37816771
2023 NAT10 Is Involved in Cardiac Remodeling Through ac4C-Mediated Transcriptomic Regulation. Circulation research 68 37955115
2023 Role of NAT10-mediated ac4C-modified HSP90AA1 RNA acetylation in ER stress-mediated metastasis and lenvatinib resistance in hepatocellular carcinoma. Cell death discovery 65 36765042
2023 Emerging roles of RNA ac4C modification and NAT10 in mammalian development and human diseases. Pharmacology & therapeutics 63 38065232
2023 Maternal NAT10 orchestrates oocyte meiotic cell-cycle progression and maturation in mice. Nature communications 61 37349316
2022 The LINC00623/NAT10 signaling axis promotes pancreatic cancer progression by remodeling ac4C modification of mRNA. Journal of hematology & oncology 58 35978332
2023 NAT10 regulates the LPS-induced inflammatory response via the NOX2-ROS-NF-κB pathway in macrophages. Biochimica et biophysica acta. Molecular cell research 57 37307924
2023 NAT10-mediated N4-acetylcytidine mRNA modification regulates self-renewal in human embryonic stem cells. Nucleic acids research 56 37497776
2022 NAT10 regulates mitotic cell fate by acetylating Eg5 to control bipolar spindle assembly and chromosome segregation. Cell death and differentiation 54 35210604
2022 NAT10: An RNA cytidine transferase regulates fatty acid metabolism in cancer cells. Clinical and translational medicine 53 36149760
2018 Loss of nucleolar localization of NAT10 promotes cell migration and invasion in hepatocellular carcinoma. Biochemical and biophysical research communications 53 29634924
2024 The positive feedback loop of the NAT10/Mybbp1a/p53 axis promotes cardiomyocyte ferroptosis to exacerbate cardiac I/R injury. Redox biology 49 38583415
2019 miR-6716-5p promotes metastasis of colorectal cancer through downregulating NAT10 expression. Cancer management and research 49 31239781
2019 Recent Advances on the Structure and Function of RNA Acetyltransferase Kre33/NAT10. Cells 49 31491951
2024 Lactylation of NAT10 promotes N4-acetylcytidine modification on tRNASer-CGA-1-1 to boost oncogenic DNA virus KSHV reactivation. Cell death and differentiation 47 38879723
2017 Inhibition of NAT10 Suppresses Melanogenesis and Melanoma Growth by Attenuating Microphthalmia-Associated Transcription Factor (MITF) Expression. International journal of molecular sciences 47 28880216
2020 Targeting NAT10 Induces Apoptosis Associated With Enhancing Endoplasmic Reticulum Stress in Acute Myeloid Leukemia Cells. Frontiers in oncology 45 33425753
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
2024 NAT10/ac4C/JunB facilitates TNBC malignant progression and immunosuppression by driving glycolysis addiction. Journal of experimental & clinical cancer research : CR 42 39363363
2024 NAT10 Promotes Prostate Cancer Growth and Metastasis by Acetylating mRNAs of HMGA1 and KRT8. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 40 38922788
2024 N-acetyltransferase NAT10 controls cell fates via connecting mRNA cytidine acetylation to chromatin signaling. Science advances 39 38215194
2023 NAT10-mediated AXL mRNA N4-acetylcytidine modification promotes pancreatic carcinoma progression. Experimental cell research 39 37156457
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 39 37914704
2024 NAT10-mediated mRNA N4-acetylcytidine reprograms serine metabolism to drive leukaemogenesis and stemness in acute myeloid leukaemia. Nature cell biology 36 39506072
2024 The role and mechanism of NAT10-mediated ac4C modification in tumor development and progression. MedComm 36 39640362
2022 NAT10 Maintains OGA mRNA Stability Through ac4C Modification in Regulating Oocyte Maturation. Frontiers in endocrinology 35 35937804
2023 NAT10-mediated RNA acetylation enhances HNRNPUL1 mRNA stability to contribute cervical cancer progression. International journal of medical sciences 33 37484809
2023 The emerging roles of ac4C acetylation "writer" NAT10 in tumorigenesis: A comprehensive review. International journal of biological macromolecules 33 37926318
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) 32 38407929
2025 NAT10 promotes vascular remodelling via mRNA ac4C acetylation. European heart journal 31 39453784
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 30 38762546
2023 NAT10, an RNA Cytidine Acetyltransferase, Regulates Ferroptosis in Cancer Cells. Antioxidants (Basel, Switzerland) 29 37237981
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 29 35986334
2023 NAT10 mediated mRNA acetylation modification patterns associated with colon cancer progression and microsatellite status. Epigenetics 27 36908042
2024 NAT10 Phase Separation Regulates YTHDF1 Splicing to Promote Gastric Cancer Progression. Cancer research 26 39024555
2023 Targeting NAT10 protects against sepsis-induced skeletal muscle atrophy by inhibiting ROS/NLRP3. Life sciences 26 37467885
2024 NAT10 promotes synovial aggression by increasing the stability and translation of N4-acetylated PTX3 mRNA in rheumatoid arthritis. Annals of the rheumatic diseases 25 38724075
2024 m6A-driven NAT10 translation facilitates fatty acid metabolic rewiring to suppress ferroptosis and promote ovarian tumorigenesis through enhancing ACOT7 mRNA acetylation. Oncogene 25 39390256
2023 Activated SIRT1 contributes to DPT-induced glioma cell parthanatos by upregulation of NOX2 and NAT10. Acta pharmacologica Sinica 25 37277492
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) 23 35834140
2024 NAT10 inhibition promotes ac4C-dependent ferroptosis to counteract sorafenib resistance in nasopharyngeal carcinoma. Cancer science 22 39038928
2023 Neutrophil extracellular traps promote gastric cancer cell metastasis via the NAT10-mediated N4-acetylcytidine modification of SMYD2. Cellular signalling 22 38110168
2020 Remodelin, an inhibitor of NAT10, could suppress hypoxia-induced or constitutional expression of HIFs in cells. Molecular and cellular biochemistry 22 32529496
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) 21 39985269
2024 CLIC3 interacts with NAT10 to inhibit N4-acetylcytidine modification of p21 mRNA and promote bladder cancer progression. Cell death & disease 21 38182571
2024 Exosomal NAT10 from esophageal squamous cell carcinoma cells modulates macrophage lipid metabolism and polarization through ac4C modification of FASN. Translational oncology 21 38692194
2025 A critical role of N4-acetylation of cytidine in mRNA by NAT10 in T cell expansion and antiviral immunity. Nature immunology 19 40045031
2025 Acetyltransferase NAT10 inhibits T-cell immunity and promotes nasopharyngeal carcinoma progression through DDX5/HMGB1 axis. Journal for immunotherapy of cancer 18 39939141
2024 Ropinirole suppresses LPS-induced periodontal inflammation by inhibiting the NAT10 in an ac4C-dependent manner. BMC oral health 18 38689229
2024 Targeting the NAT10/NPM1 axis abrogates PD-L1 expression and improves the response to immune checkpoint blockade therapy. Molecular medicine (Cambridge, Mass.) 17 38243170
2024 NAT10-mediated mRNA N4-acetylcytidine modification of MDR1 and BCRP promotes breast cancer progression. Thoracic cancer 17 38409918
2024 Remodelin delays non-small cell lung cancer progression by inhibiting NAT10 via the EMT pathway. Cancer medicine 17 38826095
2024 RNPS1 stabilizes NAT10 protein to facilitate translation in cancer via tRNA ac4C modification. International journal of oral science 16 38246918
2024 NAT10-mediated ac4C acetylation of TFRC promotes sepsis-induced pulmonary injury through regulating ferroptosis. Molecular medicine (Cambridge, Mass.) 16 39251905
2023 PARP-dependent and NAT10-independent acetylation of N4-cytidine in RNA appears in UV-damaged chromatin. Epigenetics & chromatin 16 37322549
2023 NAT10 promotes the tumorigenesis and progression of laryngeal squamous cell carcinoma through ac4C modification of FOXM1 mRNA. Cancer biology & therapy 13 37948132
2023 The mechanistic role of NAT10 in cancer: Unraveling the enigmatic web of oncogenic signaling. Pathology, research and practice 13 38056132
2023 NAT10 Promotes Malignant Progression of Lung Cancer via the NF-κB Signaling Pathway. Discovery medicine 13 38058058
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 12 40261924
2024 NAT10 promotes renal ischemia-reperfusion injury via activating NCOA4-mediated ferroptosis. Heliyon 12 38312597
2024 NAT10 promotes osteoclastogenesis in inflammatory bone loss by catalyzing Fos mRNA ac4C modification and upregulating MAPK signaling pathway. Journal of advanced research 12 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 12 39392166
2024 Acetyltransferase NAT10 promotes an immunosuppressive microenvironment by modulating CD8+ T cell activity in prostate cancer. Molecular biomedicine 12 39648231
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) 11 40540648
2024 NAT10-mediated ac4C modification promotes stemness and chemoresistance of colon cancer by stabilizing NANOGP8. Heliyon 11 38726177
2024 NAT10 and cytidine acetylation in mRNA: intersecting paths in development and disease. Current opinion in genetics & development 11 38820741
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 Inhibition of tumor-intrinsic NAT10 enhances antitumor immunity by triggering type I interferon response via MYC/CDK2/DNMT1 pathway. Nature communications 10 40461504
2023 NAT10 regulates the repair of UVB-induced DNA damage and tumorigenicity. Toxicology and applied pharmacology 10 37716414
2025 N4-acetylcytidine modification of ITGB5 mRNA mediated by NAT10 promotes perineural invasion in pancreatic ductal adenocarcinoma. Journal of experimental & clinical cancer research : CR 9 40119353
2025 NAT10-mediated N4-acetylcytidine modification in KLF9 mRNA promotes adipogenesis. Cell death and differentiation 9 40123006
2025 Targeting NAT10 attenuates homologous recombination via destabilizing DNA:RNA hybrids and overcomes PARP inhibitor resistance in cancers. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy 9 40132530
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 9 40193598
2025 Effects of HALP Score, C-Reactive Protein/Albumin Ratio, and Platelet/Lymphocyte Ratio on Predicting Mortality in Geriatric Patients in the Respiratory Intensive Care Unit. Clinical interventions in aging 9 40503075
2025 Targeting the NAT10/XIST/YAP1 Axis-Mediated Vascular Abnormalization Enhances Immune Checkpoint Blockade in Gastric Cancer. International journal of biological sciences 9 40860183
2025 Targeting NAT10 Inhibits Hepatocarcinogenesis via ac4C-Mediated SMAD3 mRNA Stability. Exploration (Beijing, China) 9 41476650
2024 Dissecting the oncogenic properties of essential RNA-modifying enzymes: a focus on NAT10. Oncogene 9 38409550
2024 NAT10 promotes liver lipogenesis in mouse through N4-acetylcytidine modification of Srebf1 and Scap mRNA. Lipids in health and disease 9 39529018
2024 PCBP1/2 and TDP43 Function as NAT10 Adaptors to Mediate mRNA ac4C Formation in Mammalian Cells. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 9 39556689
2025 NAT10 inhibition alleviates astrocyte autophagy by impeding ac4C acetylation of Timp1 mRNA in ischemic stroke. Acta pharmaceutica Sinica. B 8 40487658
2025 Aging increases susceptibility to liver fibrosis through enhanced NAT10-mediated ac4C modification of TGFβ1 mRNA. Genome medicine 8 40817062
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 Mediates XPO1 mRNA N4-acetylation and Promotes Drug Resistance of Myeloma Cells. Journal of Cancer 8 39513105
2022 NAT10 and DDX21 Proteins Interact with RNase H1 and Affect the Performance of Phosphorothioate Oligonucleotides. Nucleic acid therapeutics 8 35852833

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