Affinage

METTL5

rRNA N(6)-adenosine-methyltransferase METTL5 · UniProt Q9NRN9

Length
209 aa
Mass
23.7 kDa
Annotated
2026-04-28
52 papers in source corpus 32 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

METTL5 is the dedicated N6-methyladenosine (m6A) methyltransferase for 18S ribosomal RNA, installing m6A at position A1832 within the ribosomal decoding center to modulate translation initiation and the selective translational efficiency of specific mRNAs. METTL5 requires heterodimerization with the adaptor protein TRMT112 for metabolic stability and catalytic competence; crystal structures reveal an RNA-binding mode distinct from mRNA m6A writers and an adenosine-extrusion catalytic mechanism (PMID:31328227, PMID:35033535). Loss of METTL5 reduces polysome abundance, impairs translation of functionally diverse transcripts (including FBXW7, SUZ12, ATF4, CXCL16, SEPHS2, and spermiogenesis factors), and thereby disrupts stem cell pluripotency, neuronal development, cardiac homeostasis, spermatogenesis, and anti-tumor immune evasion (PMID:32217665, PMID:32783360, PMID:35295259, PMID:40783785, PMID:41042068). Bi-allelic loss-of-function mutations in METTL5 cause autosomal recessive intellectual disability with microcephaly in humans (PMID:31564433, PMID:35033535).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2019 High

    Establishing METTL5 as the 18S rRNA m6A methyltransferase and defining its obligate partnership with TRMT112 resolved the long-standing question of which enzyme installs m6A on eukaryotic ribosomal RNA.

    Evidence X-ray crystallography of METTL5–TRMT112, in vitro methyltransferase assays, and cellular stability assays

    PMID:31328227

    Open questions at the time
    • No substrate RNA-bound co-crystal structure
    • Mechanism of substrate recognition on intact ribosomal subunits not resolved
    • Regulation of METTL5 expression or activity unknown
  2. 2019 Medium

    Identification of bi-allelic METTL5 loss-of-function variants in families with intellectual disability and microcephaly established the first human disease link for this rRNA methyltransferase, and localization studies placed METTL5 in both nuclear and synaptic compartments of hippocampal neurons.

    Evidence Exome sequencing of affected families, immunofluorescence in hippocampal neurons, zebrafish morpholino knockdown recapitulating microcephaly

    PMID:31564433

    Open questions at the time
    • Zebrafish knockdown does not prove causality in humans without rescue
    • Precise neural cell-type requirement unresolved
    • How rRNA m6A loss leads to microcephaly mechanistically unclear
  3. 2020 High

    Demonstrating that Mettl5 knockout in mouse ESCs reduces global translation, causes spontaneous loss of pluripotency, and impairs differentiation — with FBXW7 identified as a translationally regulated target whose reduced expression leads to c-MYC accumulation — connected the rRNA modification to specific mRNA translational control and stem cell biology.

    Evidence Mettl5 KO mESCs, polysome profiling, FBXW7/c-MYC western blots, translation rate measurements across multiple labs

    PMID:32217665 PMID:32783360

    Open questions at the time
    • Whether translational selectivity is direct (codon usage, mRNA structure) or indirect not distinguished
    • Genome-wide ribosome profiling in mESCs not performed at this stage
  4. 2020 High

    Biochemical substrate specificity assays and polysome profiling showed METTL5 has strong preference for 18S A1832 and that this modification facilitates translation initiation, likely through conformational changes in the decoding center — providing the first mechanistic link between the specific modification site and ribosome function.

    Evidence Methyltransferase substrate specificity assays, p70-S6K phosphorylation, polysome profiling, structural modeling with yeast ribosome

    PMID:33357433

    Open questions at the time
    • No direct cryo-EM structure of m6A1832-containing human ribosome
    • Whether p70-S6K activation is a direct or indirect consequence remains uncertain
  5. 2020 High

    Conservation of the METTL5–TRMT112 partnership and its specific role in 18S rRNA m6A deposition was confirmed in Drosophila, where loss causes behavioral deficits without affecting rRNA maturation, demonstrating an evolutionarily conserved post-transcriptional role in neuronal function.

    Evidence Drosophila RNAi, mass spectrometry of RNA modifications, co-IP, behavioral assays

    PMID:32350990

    Open questions at the time
    • Specific neuronal mRNA targets in Drosophila not identified
    • Whether behavioral phenotype maps to specific brain regions unknown
  6. 2022 High

    Disease-associated METTL5 mutations were shown to disrupt the METTL5–TRMT112 interaction, providing a direct molecular mechanism linking human microcephaly/intellectual disability variants to loss of rRNA methyltransferase function.

    Evidence In vitro methyltransferase assay, co-IP with disease mutants, Mettl5 KO mice, ribosome profiling

    PMID:35033535

    Open questions at the time
    • Patient-derived cells not yet tested
    • Whether partial loss of TRMT112 interaction produces intermediate phenotypes unknown
  7. 2021 Medium

    Extension of METTL5's translational regulatory role to cancer showed it enhances c-Myc translation in pancreatic cancer and USP5 translation in hepatocellular carcinoma (the latter stabilizing c-Myc protein), revealing convergent oncogenic mechanisms operating through distinct translational targets in different tumor types.

    Evidence Polysome profiling, siRNA/overexpression, m6A quantification in pancreatic cancer; GST pulldown, ubiquitination assays, polysome profiling in HCC

    PMID:34970694 PMID:36602428

    Open questions at the time
    • Whether METTL5 directly methylates mRNA m6A sites (as suggested for c-Myc mRNA) or acts solely through 18S rRNA modification is unresolved
    • Single-lab studies in each cancer type
  8. 2022 Medium

    Identifying SUZ12 as a METTL5-dependent translational target in cardiac hypertrophy, with cardiac-specific Mettl5 KO mice showing enhanced pathological remodeling, extended the gene's physiological role beyond stem cells and neurons to the heart.

    Evidence Cardiac-specific Mettl5 conditional KO mice, polysome profiling, pressure-overload model

    PMID:35295259

    Open questions at the time
    • Direct ribosome profiling in cardiomyocytes not performed
    • Whether SUZ12 is the sole effector in cardiac hypertrophy not established
  9. 2023 Medium

    Discovery that METTL5 loss inhibits translation of G-quadruplex-containing mRNAs (enriched in TGF-β pathway genes) in cholangiocarcinoma revealed a structural feature of mRNAs that may explain METTL5's selective translational effects.

    Evidence Ribosome profiling, liver-specific Mettl5 KO and overexpression mouse models, G-quadruplex mRNA translation analysis

    PMID:37735874

    Open questions at the time
    • G-quadruplex selectivity not validated by mutation of G4 structures in individual mRNAs
    • Whether this selectivity applies broadly or is context-specific unknown
  10. 2025 Medium

    Multiple studies established METTL5 as a regulator of anti-tumor immunity: loss of METTL5 reduces ATF4 translation (enhancing ferroptosis sensitivity and T cell killing in ovarian cancer) and reduces CXCL16 translation (increasing CD8+ T cell infiltration in cholangiocarcinoma), positioning METTL5 as a potential immunotherapy target.

    Evidence METTL5 KO tumor models, ATF4 rescue epistasis, scRNA-seq/scTCR-seq, liver-specific KO mice, LNP-siRNA combined with PD-1 blockade

    PMID:41042068 PMID:41431992

    Open questions at the time
    • Whether neoantigen generation from reduced translation fidelity contributes to immune phenotype in these models not tested in peer-reviewed work
    • Therapeutic window for METTL5 inhibition not established
  11. 2025 Medium

    METTL5-null mutations cause male infertility (oligoasthenoteratozoospermia) in humans and mice by compromising translational efficiency of spermiogenesis-specific mRNAs without affecting global translation, demonstrating tissue-specific translational selectivity.

    Evidence Human genetics, Mettl5 KO mice, ribosome profiling of spermatogenic cells

    PMID:40783785

    Open questions at the time
    • How transcript-specific selectivity is achieved in germ cells not mechanistically resolved
    • Whether female fertility is also affected not fully characterized
  12. 2025 High

    A co-crystal structure of a covalent stereoprobe bound at TRMT112 C100 within the METTL5–TRMT112 complex — a site templated exclusively by the heterodimer interface — revealed the first allosteric modulator of METTL5 catalytic activity and demonstrated that the complex is druggable at a composite pocket.

    Evidence Chemical proteomics, X-ray co-crystal structure, in vitro methyltransferase activity assay

    PMID:41507545

    Open questions at the time
    • Allosteric agonism rather than inhibition was observed; therapeutic inhibitors not yet available
    • Cellular efficacy of stereoprobes on endogenous rRNA m6A not demonstrated
    • Selectivity over other TRMT112 complexes in cells not fully validated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: (1) the structural basis by which m6A1832 in the decoding center confers transcript-selective translation, (2) whether reported METTL5 effects on mRNA m6A/stability reflect direct mRNA methylation or are indirect consequences of rRNA modification, and (3) how METTL5 activity is regulated in different tissues and developmental contexts.
  • No cryo-EM structure of m6A1832-modified human ribosome in translating state
  • No consensus on whether METTL5 has any direct mRNA methyltransferase activity
  • Upstream signals controlling METTL5 expression/stability beyond TRIM28 are poorly defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 7
Localization
GO:0005829 cytosol 2 GO:0005634 nucleus 1
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-392499 Metabolism of proteins 5 R-HSA-8953854 Metabolism of RNA 3
Partners
TRIM28TRMT112USP21
Complex memberships
METTL5–TRMT112 heterodimer

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2019 METTL5 is the 18S rRNA m6A methyltransferase responsible for N6-methyladenosine modification of human 18S rRNA, and must form a heterodimeric complex with TRMT112 to gain metabolic stability in cells. The first atomic resolution structure of METTL5-TRMT112 was solved, revealing an RNA-binding mode distinct from other m6A methyltransferases, and suggesting an adenosine extrusion mechanism analogous to DNA methyltransferases. In vitro methyltransferase assay, co-immunoprecipitation, X-ray crystallography, cellular stability assays Nucleic acids research High 31328227
2020 METTL5 catalyzes m6A modification at position A1832 of 18S rRNA in vivo and in vitro. Loss of Mettl5 in mouse embryonic stem cells reduces global translation rate, causes spontaneous loss of pluripotency, and compromises differentiation potential. In vitro methyltransferase assay, Mettl5 knockout mESCs, polysome profiling, translation rate measurement Genes & development High 32217665
2020 METTL5 shows strong substrate preference for 18S A1832 and promotes p70-S6K activation and proper translation initiation; loss of METTL5 significantly reduces polysome abundance. Structural comparison with unmodified yeast ribosomes indicates the m6A modification may facilitate mRNA binding by inducing conformation changes in the decoding center. Methyltransferase substrate specificity assay, polysome profiling, p70-S6K activation assay, structural modeling Cell reports High 33357433
2020 Deletion of Mettl5 in mouse embryonic stem cells impairs efficient translation of FBXW7, a key regulator of cell differentiation, leading to c-MYC accumulation and delayed differentiation onset. METTL5 methylates 18S rRNA both in vivo and in vitro. Mettl5 knockout mESCs, polysome profiling, western blotting for FBXW7 and c-MYC, in vitro methyltransferase assay EMBO reports High 32783360
2020 Drosophila CG9666 (ortholog of human METTL5) directly interacts with CG12975 (ortholog of TRMT112) to deposit m6A specifically on 18S rRNA; depletion of CG9666 abolishes 18S rRNA m6A without compromising rRNA maturation, but impairs fly behavior. RNAi screen, mass spectrometry of RNA modifications, co-immunoprecipitation, behavioral assays EMBO reports High 32350990
2022 The METTL5-TRMT112 complex installs m6A at position A1832 of human 18S rRNA; TRMT112 is required for METTL5 stability; human METTL5 mutations associated with microcephaly and intellectual disability disrupt the METTL5-TRMT112 interaction. Loss of METTL5 in human cancer cell lines and mice regulates gene expression at the translational level. In vitro methyltransferase assay, co-immunoprecipitation, Mettl5 knockout mice, ribosome profiling The Journal of biological chemistry High 35033535
2019 Bi-allelic frameshift variants in METTL5 cause intellectual disability and microcephaly; METTL5 protein is enriched in the nucleus and synapses of hippocampal neurons; truncating variants do not affect localization but alter protein expression levels. Mettl5 knockdown in zebrafish causes microcephaly. Exome sequencing, transfection of orthologous cells, immunofluorescence localization in hippocampal neurons, zebrafish knockdown American journal of human genetics Medium 31564433
2020 Mettl5 knockout in mESCs leads to abnormal craniofacial and nervous development; the METTL5 protein complex predominantly interacts with RNA binding proteins and ribosome proteins. Mettl5 knockout mice exhibit intellectual disability and impaired myelination in brain. Co-immunoprecipitation/mass spectrometry of METTL5 protein complex, Mettl5 knockout mice, behavioral testing, myelin staining Genes & diseases Medium 35005123
2021 METTL5 promotes pancreatic cancer cell proliferation, migration, and invasion through increased c-Myc translation. m6A modifications at the 5'UTR and CDS (near 5'UTR) of c-Myc mRNA are critical for this specific translational regulation. METTL5 and its cofactor TRMT112 synergistically promote cancer progression. Polysome profiling, siRNA knockdown/overexpression, m6A quantification, in vitro functional assays International journal of oncology Medium 34970694
2022 METTL5-mediated 18S rRNA m6A modification modulates translation of SUZ12 (a core PRC2 component) to regulate transcriptomic shifts during cardiac hypertrophy. Cardiac-specific METTL5 knockout mice show enhanced pressure overload-induced hypertrophy. Cardiac-specific Mettl5 conditional knockout mice, polysome profiling, western blotting, cardiomyocyte gain- and loss-of-function assays Frontiers in cardiovascular medicine Medium 35295259
2023 METTL5 controls USP5 translation, which in turn stabilizes c-Myc by inhibiting K48-linked polyubiquitination via USP5 binding to c-Myc. CREB1/P300 acts as a transcriptional regulator promoting METTL5 transcription in HCC. GST pulldown, co-immunoprecipitation, polysome profiling, RNA sequencing, luciferase reporter assay, ubiquitination assay Cancer communications Medium 36602428
2023 METTL5 depletion impairs 18S rRNA m6A modification, hampers ribosome synthesis, and inhibits translation of G-quadruplex-containing mRNAs enriched in TGF-β pathway in intrahepatic cholangiocarcinoma. Liver-specific METTL5 knockout and overexpression ICC mouse models confirmed these effects. Loss- and gain-of-function in vitro and in vivo assays, ribosome profiling, m6A quantification, G-quadruplex mRNA translation analysis, liver-specific KO mouse models Molecular therapy Medium 37735874
2022 METTL5 regulates cranial suture fusion by controlling Wnt signaling; Mettl5 knockout mice show poor ossification, widened cranial sutures, increased proliferation and decreased osteogenic differentiation of suture mesenchymal stem cells. Mettl5 knockout mice, cell proliferation and differentiation assays, Wnt signaling pathway analysis Fundamental research Medium 38933773
2025 METTL5 knockout in ovarian cancer disrupts ATF4 translation by altering 18S rRNA m6A levels, leading to downregulation of SLC7A11 and SLC3A2, thus enhancing ferroptosis sensitivity and tumor susceptibility to T cell-mediated antitumor immunity. ATF4 overexpression or ferroptosis inhibition reverses METTL5-KO immune-sensitive phenotypes. Genome-wide immune screens, METTL5 KO in cancer cells, rescue experiments with ATF4 overexpression, ferroptosis inhibitor, in vivo tumor models Advanced science Medium 41042068
2025 TRIM28 mediates Mettl5 ubiquitination and degradation in CD4+ T cells; reduced Mettl5 levels lead to hypomethylation at the Gata3 promoter and increased GATA3 transcription, promoting Th2 polarization. In airway allergy, Mettl5 also recruits USP21 to deubiquitinate GATA3, boosting IL-4 expression in M2 macrophages. Chromatin immunoprecipitation assay, co-immunoprecipitation, ubiquitination assay, Mettl5 conditional KO in macrophages/T cells, mouse allergy model Frontiers in immunology / Cellular signalling Medium 40089091 40391221
2025 METTL5 depletion reduces selenophosphate synthetase 2 (SEPHS2) translation efficiency, leading to diminished selenoprotein synthesis and increased ROS, inducing apoptosis in multiple myeloma. Salvianolic acid C (SAC) was identified as a METTL5 inhibitor. Mettl5 knockdown, ribosome profiling/translation efficiency measurement, ROS assay, in vitro and in vivo myeloma models, drug inhibitor assay Cell death & disease Medium 40750759
2025 METTL5-mediated 18S rRNA m6A modification promotes translation of CXCL16, enabling immune evasion in intrahepatic cholangiocarcinoma by excluding CD8+ T cells. Mettl5 liver-specific KO increases CD8+ T cell infiltration and reduces immunosuppressive tumor-associated macrophages. Liver-specific Mettl5 conditional KO mice, scRNA-seq, scTCR-seq, adoptive macrophage transfer, lipid nanoparticle siRNA delivery combined with PD-1 blockade Advanced science Medium 41431992
2024 METTL5 upregulation promotes NRF2 mRNA stability; IGF2BP1 mediates NRF2 mRNA stability via the METTL5/m6A/NRF2 axis, thereby inactivating ferroptosis and repressing anti-tumor immunity in gastric cancer. mRNA stability assay, RNA immunoprecipitation, loss-of-function experiments, co-culture with PBMCs Cell death discovery Low 39261486
2024 METTL5 positively regulates TPRKB expression by enhancing TPRKB mRNA stability via m6A modification in hepatocellular carcinoma. mRNA stability assay, METTL5 knockdown, rescue experiments with TPRKB overexpression Experimental cell research Low 39182664
2025 METTL5-mediated m6A modification enhances UBE3C mRNA stability by enabling YTHDF1 to bind and protect the modified mRNA from degradation; UBE3C then promotes ubiquitination and degradation of AHNAK, suppressing ferroptosis in osteosarcoma. mRNA stability assay, RIP for YTHDF1 binding, UBE3C knockdown/overexpression, ferroptosis assay, Co-IP Journal of molecular histology Low 40696164
2025 METTL5 promotes HCC recurrence after thermal ablation by enhancing PEX16 translation, which promotes peroxisomal biogenesis and β-oxidation of very long-chain fatty acids, thereby facilitating mitochondrial respiration under heat stress. Insufficient RFA in vitro and in vivo models, translation efficiency analysis, peroxisome biogenesis assay, fatty acid oxidation assay Molecular therapy Low 41234012
2024 METTL5 promotes corticospinal tract sprouting after traumatic brain injury by increasing translation efficiency of Cfl1 (cofilin) and Inpp5k, leading to cofilin activation, actin polymerization, and axon outgrowth. METTL5 overexpression in corticospinal neurons, ribosome profiling (translation efficiency), anterograde axonal tracing, cofilin activity assay Experimental neurology Medium 39406306
2025 Bicyclopyrrolidine acrylamide stereoprobes react covalently with C100 of TRMT112 exclusively within the METTL5-TRMT112 complex (not other TRMT112 complexes). Co-crystal structure revealed a composite binding pocket templated by METTL5 at TRMT112's C100; stereoprobe binding causes allosteric agonism of METTL5 catalytic activity. Chemical proteomics, co-crystal structure (X-ray crystallography), in vitro methyltransferase activity assay, recombinant protein binding assays Nature chemical biology / bioRxiv High 40475643 41507545
2024 Drosophila Mettl5 regulates sleep by controlling translational output of proteasome components and clock genes; loss of Mettl5 or Trmt112 increases PERIOD protein levels, causing sleep phenotypes. Mettl5 functions predominantly within neurons and glia. Drosophila Mettl5 mutants, rescue experiments with tissue-specific expression, RNA-seq and Ribo-seq, PERIOD protein quantification bioRxivpreprint Medium bio_10.1101_2024.10.24.620129
2025 METTL5 deficiency decreases translation fidelity of ribosomes, increases non-canonical translation products, and generates tumor neoantigens that stimulate CD8+ T cell infiltration and TCR repertoire diversity in murine tumor models. This effect depends on intact antigen presentation pathways. Mettl5 knockout tumor models, antigen presentation pathway epistasis, TCR-seq, CD8+ T cell infiltration analysis bioRxivpreprint Medium bio_10.1101_2025.06.06.658288
2025 METTL5 promotes METTL5-mediated m6A modification of 18S rRNA, which modulates MGST1 protein expression through its N6-methyladenosine catalytic function, suppressing ferroptosis in HCC. Tandem mass tagging proteomic quantification, METTL5 knockdown, ferroptosis assay, western blotting Molecular and cellular biochemistry Low 41557129
2025 Cortical organoids from METTL5-KO human iPSCs show delayed neural stem cell proliferation and neuronal differentiation timing. CHCHD2, a nuclear-encoded mitochondrial gene, is significantly downregulated; overexpression of CHCHD2 rescues proliferation defects of METTL5-KO neural progenitors, linking METTL5-mediated rRNA modification to mitochondrial metabolism in human neurodevelopment. Human iPSC-derived cortical organoids, METTL5 KO, transcriptomic analysis, CHCHD2 rescue experiments bioRxivpreprint Medium 40672170
2025 METTL5 promotes OSCC progression via m6A-mediated 18S rRNA methylation that enhances translation of CCND3 (cyclin D3), as identified by ribosome nascent-chain complex-bound mRNA sequencing (RNC-seq). METTL5 knockout, RNC-seq (ribosome nascent-chain complex-bound mRNA sequencing), in vitro and in vivo functional assays Oncology letters Medium 41743013
2025 METTL5 deficiency in humans and mice (null mutation of Mettl5) leads to male infertility (oligoasthenoteratozoospermia) by compromising translational efficiency of mRNAs encoding proteins critical for spermiogenesis (Gk2, Akap4, Fsip2, Odf2, Pgk2) without affecting global translation. Human genetics (variant identification in infertility patients), Mettl5 knockout mice, ribosome profiling for translation efficiency, sperm functional analysis Molecular therapy Medium 40783785
2024 METTL5 interacts with IGF2BP3 in NSCLC cells, and IGF2BP3 expression is regulated downstream of METTL5; IGF2BP3 overexpression rescues METTL5 knockdown-impaired cell proliferation, placing IGF2BP3 in the METTL5 pathway. Co-immunoprecipitation, knockdown/overexpression rescue experiments, in vivo tumor model Genetic testing and molecular biomarkers Low 39023781

Source papers

Stage 0 corpus · 52 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 The human 18S rRNA m6A methyltransferase METTL5 is stabilized by TRMT112. Nucleic acids research 416 31328227
2023 METTL5 stabilizes c-Myc by facilitating USP5 translation to reprogram glucose metabolism and promote hepatocellular carcinoma progression. Cancer communications (London, England) 140 36602428
2020 The rRNA m6A methyltransferase METTL5 is involved in pluripotency and developmental programs. Genes & development 122 32217665
2020 Ribosome 18S m6A Methyltransferase METTL5 Promotes Translation Initiation and Breast Cancer Cell Growth. Cell reports 121 33357433
2019 Bi-allelic Variants in METTL5 Cause Autosomal-Recessive Intellectual Disability and Microcephaly. American journal of human genetics 78 31564433
2020 The 18S rRNA m6 A methyltransferase METTL5 promotes mouse embryonic stem cell differentiation. EMBO reports 67 32783360
2020 The 18S ribosomal RNA m6 A methyltransferase Mettl5 is required for normal walking behavior in Drosophila. EMBO reports 63 32350990
2022 The METTL5-TRMT112 N6-methyladenosine methyltransferase complex regulates mRNA translation via 18S rRNA methylation. The Journal of biological chemistry 60 35033535
2021 Ribosome 18S m6A methyltransferase METTL5 promotes pancreatic cancer progression by modulating c‑Myc translation. International journal of oncology 49 34970694
2023 METTL5-mediated 18S rRNA m6A modification promotes oncogenic mRNA translation and intrahepatic cholangiocarcinoma progression. Molecular therapy : the journal of the American Society of Gene Therapy 40 37735874
2020 Mettl5 mediated 18S rRNA N6-methyladenosine (m6A) modification controls stem cell fate determination and neural function. Genes & diseases 40 35005123
2022 The emerging importance of METTL5-mediated ribosomal RNA methylation. Experimental & molecular medicine 37 36266443
2022 Loss of m6A Methyltransferase METTL5 Promotes Cardiac Hypertrophy Through Epitranscriptomic Control of SUZ12 Expression. Frontiers in cardiovascular medicine 27 35295259
2022 Knockdown of METTL5 inhibits the Myc pathway to downregulate PD-L1 expression and inhibits immune escape of hepatocellular carcinoma cells. Journal of chemotherapy (Florence, Italy) 23 36369791
2024 N6-methyladenosine (m6A) writer METTL5 represses the ferroptosis and antitumor immunity of gastric cancer. Cell death discovery 15 39261486
2022 METTL5 regulates cranial suture fusion via Wnt signaling. Fundamental research 13 38933773
2024 The m6A methyltransferase METTL5 promotes neutrophil extracellular trap network release to regulate hepatocellular carcinoma progression. Cancer medicine 12 38613157
2024 METTL5 enhances the mRNA stability of TPRKB through m6A modification to facilitate the aggressive phenotypes of hepatocellular carcinoma cell. Experimental cell research 8 39182664
2021 Analysis of the role of METTL5 as a hub gene in lung adenocarcinoma based on a weighted gene co-expression network. Mathematical biosciences and engineering : MBE 8 34517547
2022 Inhibition of METTL5 improves preimplantation development of mouse somatic cell nuclear transfer embryos. Reproduction (Cambridge, England) 7 36111643
2024 METTL5-mediated 18S rRNA m6A modification promotes corticospinal tract sprouting after unilateral traumatic brain injury. Experimental neurology 6 39406306
2024 METTL5 promotes cell proliferation, invasion, and migration by up-regulating Toll-like receptor 8 expression in colorectal cancer. World journal of gastrointestinal oncology 5 38764815
2024 METTL5 promotes gastric cancer progression via sphingomyelin metabolism. World journal of gastrointestinal oncology 5 38764837
2023 A novel METTL5 variant disrupting a donor splice site leads to primary microcephaly-related intellectual disability in an Iranian family: clinical features and literature review. Journal of genetics 5 37731250
2022 Three Afghani siblings with a novel homozygous variant and further delineation of the clinical features of METTL5 related intellectual disability syndrome. The Turkish journal of pediatrics 5 36305450
2024 METTL5: A Potential Biomarker for Nonsmall Cell Lung Cancer That Promotes Cancer Cell Proliferation by Interacting with IGF2BP3. Genetic testing and molecular biomarkers 4 39023781
2025 Scutellarin suppresses ovarian cancer progression by targeting METTL5. Scientific reports 3 40425707
2025 METTL5 regulates SEPHS2-mediated selenoprotein synthesis to promote multiple myeloma survival and progression. Cell death & disease 3 40750759
2025 Tumor Intrinsic METTL5 Modulates ATF4 Translation to Prevent T Cell-Induced Ferroptosis in Ovarian Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 3 41042068
2024 Biological significance of METTL5 in atherosclerosis: comprehensive analysis of single-cell and bulk RNA sequencing data. Aging 3 38663914
2024 METTL4 and METTL5 as biomarkers for recurrence-free survival in hepatocellular carcinoma patients. Future oncology (London, England) 3 39706798
2026 Complexoform-restricted covalent TRMT112 ligands that allosterically agonize METTL5. Nature chemical biology 2 41507545
2025 METTL5 Promotes Tumor Progression in Oral Squamous Cell Carcinoma by Activating the Myc Pathway. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 2 39870169
2025 The human 18S rRNA m6A methyltransferase METTL5 promotes tumorigenesis via DEPDC1 in lung squamous cell carcinoma. Frontiers in oncology 2 40018408
2025 Modulation of Mettl5 alleviates airway allergy by regulating the epigenetic profile of M2 macrophages. Cellular signalling 2 40089091
2025 Microcephaly-related global developmental delay caused by a pathogenic METTL5 splicing mutation in a Chinese family. Journal of human genetics 2 40500307
2025 METTL5-mediated 18S rRNA m6A modification enhances ribosome assembly and ABA response in Arabidopsis. iMeta 2 40860432
2025 TRIM28 mediates Mettl5 ubiquitination to promotes Th2 polarization. Frontiers in immunology 1 40391221
2025 Complexoform-restricted covalent TRMT112 ligands that allosterically agonize METTL5. bioRxiv : the preprint server for biology 1 40475643
2025 Cortical organoids reveal human-specific roles of METTL5 in neurodevelopment via regulation of CHCHD2. bioRxiv : the preprint server for biology 1 40672170
2025 METTL5-mediated m6A modification of UBE3C promotes osteosarcoma progression by suppressing ferroptosis via inducing AHNAK ubiquitination. Journal of molecular histology 1 40696164
2025 METTL5 deficiency induces oligoasthenoteratozoospermia via impaired 18S rRNA m6A methylation in humans and mice. Molecular therapy : the journal of the American Society of Gene Therapy 1 40783785
2025 METTL5 Enables Immune Evasion of Liver Cancer via Chemokine mRNA Translation Regulation. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 1 41431992
2024 Gene polymorphisms of METTL5 and METTL16 are related to epithelial ovarian cancer risk in South China: A three-center case-control study. Journal of Cancer 1 38370381
2026 METTL5 promotes tumor progression and ferroptosis resistance via MGST1 in HCC. Molecular and cellular biochemistry 0 41557129
2026 METTL5-mediated m6A modification of 18S rRNA drives oral squamous cell carcinoma progression by enhancing CCND3 translation. Oncology letters 0 41743013
2026 Esketamine Suppresses Astrocyte-Driven Neuroinflammation in Traumatic Brain Injury via the METTL5/c-Myc/PD-L1. Neurochemical research 0 41824127
2026 Heterozygous loss-of-function variant in METTL5 is associated with intellectual disability. Human molecular genetics 0 41873838
2025 Correction to: METTL5 promotes cell proliferation, invasion, and migration by up-regulating Toll-like receptor 8 expression in colorectal cancer. World journal of gastrointestinal oncology 0 39958545
2025 METTL5 promotes fatty acid metabolism by modulating peroxisome to induce hepatocellular carcinoma recurrence after thermal ablation. Molecular therapy : the journal of the American Society of Gene Therapy 0 41234012
2025 Functional Interpretation of a Novel Homozygous METTL5 Variant Associated with ADHD and Neurodevelopmental Abnormalities: A Case Report and Literature Review. Genes 0 41465175
2025 METTL5 in physiology and pathology: mechanisms and implications. Frontiers in cell and developmental biology 0 41487998