Affinage

METTL5

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

Length
209 aa
Mass
23.7 kDa
Annotated
2026-06-10
55 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: UniProt preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

METTL5 is the m6A methyltransferase that installs N6-methyladenosine at position A1832 of 18S rRNA within the ribosomal decoding center, functioning as an obligate heterodimer with the adaptor TRMT112, which confers its metabolic stability; the crystal structure reveals an RNA-binding mode distinct from other m6A methyltransferases and an adenosine-extrusion catalytic mechanism (PMID:31328227, PMID:32217665, PMID:35033535). This single rRNA modification tunes the translational machinery rather than acting on mRNA directly: loss of METTL5 reduces global translation, polysome abundance, and p70-S6K activation, and direct RNA sequencing finds no evidence of METTL5-dependent mRNA m6A, confining its catalytic activity to rRNA (PMID:33357433, PMID:42181001). Through the modified decoding center, METTL5 selectively governs the translation efficiency of specific transcripts—including FBXW7, SUZ12, SEPHS2, OSER1, CXCL16, and spermiogenesis mRNAs—thereby controlling stem cell pluripotency and differentiation, neural and craniofacial development, cardiac homeostasis, spermatogenesis, and the tumor immune microenvironment (PMID:32217665, PMID:32783360, PMID:35295259, PMID:40750759, PMID:41431992, PMID:40783785, PMID:42100868). Bi-allelic loss-of-function variants in METTL5 cause autosomal-recessive intellectual disability and microcephaly, and disease-associated mutations act by disrupting the METTL5–TRMT112 interaction (PMID:35033535, PMID:31564433). A composite pocket templated jointly by METTL5 and TRMT112-C100 is selectively targetable by covalent stereoprobes that allosterically agonize METTL5 activity, defining a chemical handle unique to the active complex (PMID:41507545).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2019 High

    Established the identity and obligate cofactor of the enzyme: METTL5 is the writer of 18S rRNA m6A and depends on TRMT112 binding for stability, settling what protein performs this modification and how it is structurally organized.

    Evidence Biochemical methyltransferase assay, atomic-resolution crystal structure of METTL5-TRMT112, cellular stability assays

    PMID:31328227

    Open questions at the time
    • Did not place the modification in a translational phenotype
    • Catalytic adenosine-extrusion mechanism inferred from structure, not directly visualized in catalysis
  2. 2019 Medium

    Linked METTL5 loss to human disease, answering whether the modification matters physiologically: bi-allelic frameshift variants cause recessive intellectual disability and microcephaly.

    Evidence Exome sequencing with segregation, immunostaining in hippocampal neurons, zebrafish morpholino knockdown

    PMID:31564433

    Open questions at the time
    • Did not connect disease variants to a specific molecular defect in the complex
    • Morpholino knockdown carries off-target risk
  3. 2020 High

    Defined the precise substrate site (A1832) and the consequence of its loss, showing the modification controls global translation rate, pluripotency, and decoding-center conformation.

    Evidence In vitro methyltransferase assays, Mettl5 KO mESCs, polysome profiling, p70-S6K assays, structural comparison with yeast ribosome

    PMID:32217665 PMID:33357433

    Open questions at the time
    • Decoding-center conformational change inferred from comparison to yeast, not human ribosome structure
    • Which specific mRNAs are translationally affected not yet defined
  4. 2020 High

    Demonstrated cross-species conservation of the mechanism, establishing the METTL5-TRMT112 ortholog pair as the rRNA writer in Drosophila and dissociating the modification from rRNA maturation.

    Evidence RNAi screen, m6A detection on 18S rRNA, direct interaction with Drosophila TRMT112 ortholog, behavioral assays

    PMID:32350990

    Open questions at the time
    • Behavioral phenotype mechanism not resolved at molecular level
  5. 2020 High

    Introduced selective translation as the operative mechanism, showing METTL5 loss specifically lowers FBXW7 translation and elevates its substrate c-MYC to delay differentiation.

    Evidence Mettl5 KO mESCs, FBXW7/c-MYC protein measurements, differentiation rescue

    PMID:32783360

    Open questions at the time
    • Why FBXW7 is selectively sensitive to A1832 m6A not mechanistically explained
  6. 2022 High

    Connected disease variants to the molecular lesion and extended phenotypes in vivo, showing microcephaly/ID mutations disrupt the METTL5-TRMT112 interaction and KO mice have reduced body size and metabolic defects.

    Evidence In vitro reconstitution with METTL5-TRMT112, disease-variant interaction assays, KO mouse and cell translational profiling

    PMID:35033535

    Open questions at the time
    • Range of mutation-affected interactions beyond TRMT112 not surveyed
  7. 2022 Medium

    Expanded the program of selectively translated targets across tissues, defining SUZ12 (cardiac), Wnt signaling (cranial sutures), and myelination-linked roles in disease and development.

    Evidence Tissue-specific KO mouse models (cardiac, suture MSC), SUZ12 and Wnt pathway assays, myelination analysis

    PMID:35005123 PMID:35295259 PMID:38933773

    Open questions at the time
    • Each target characterized in single labs
    • Direct demonstration that SUZ12/Wnt effects are 18S-m6A-dependent partial
  8. 2024 Medium

    Established METTL5 as a regulator of tumor immunity and redox biology through selective translation, linking it to ATF4/ferroptosis, CXCL16-driven CD8+ T cell recruitment, SEPHS2/selenoprotein synthesis, and OSER1-mediated antioxidant capacity.

    Evidence Genome-wide immune screens, tissue-specific KO/OE mouse models, ribosome profiling, ATF4 and ferroptosis rescue, scRNA/scTCR-seq, NAC rescue

    PMID:40750759 PMID:41042068 PMID:41431992 PMID:42100868

    Open questions at the time
    • Mechanistic basis for selectivity toward each target transcript unresolved
    • Single-lab findings per tumor context
  9. 2025 Medium

    Demonstrated tissue-specific translational substrate sets and post-translational control of METTL5, showing spermiogenesis mRNA translation defects causing infertility, and TRIM28-mediated ubiquitination as an upstream regulator of METTL5 abundance.

    Evidence Mettl5 KO mouse with ribosome profiling and sperm phenotyping, clinical variant identification; TRIM28 interaction and ubiquitination assays with ChIP

    PMID:40391221 PMID:40783785

    Open questions at the time
    • Whether TRIM28-driven Gata3 hypomethylation reflects a direct METTL5 catalytic role on DNA/promoters not established
    • Spermiogenesis selectivity mechanism unknown
  10. 2026 High

    Resolved the boundary of METTL5 catalytic activity and opened it to pharmacology: direct RNA sequencing excludes mRNA m6A as a METTL5 product, while stereoprobes reveal a composite METTL5-TRMT112 pocket that can allosterically agonize the enzyme.

    Evidence Nanopore direct RNA sequencing of KO vs WT mESCs with controls; chemical proteomics, co-crystal structure, in vitro activity assay

    PMID:41507545 PMID:42181001

    Open questions at the time
    • Several cancer studies invoking mRNA m6A by METTL5 not reconciled with the negative DRS result
    • Therapeutic consequences of allosteric agonism in vivo untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • What remains unknown: how a single 18S rRNA modification at A1832 mechanistically confers transcript-selective translation across so many distinct target mRNAs (FBXW7, SUZ12, SEPHS2, CXCL16, etc.).
  • No unifying sequence/structural feature of selectively translated mRNAs defined
  • Whether reported mRNA-m6A/reader axes reflect direct METTL5 activity remains inconsistent with direct-sequencing data

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140098 catalytic activity, acting on RNA 4 GO:0016740 transferase activity 3 GO:0003723 RNA binding 2
Localization
GO:0005840 ribosome 2 GO:0005634 nucleus 1
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-8953854 Metabolism of RNA 3
Partners
TRIM28TRMT112
Complex memberships
METTL5-TRMT112

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2019 METTL5 is the m6A methyltransferase responsible for N6-methyladenosine modification of human 18S rRNA. METTL5 must form a heterodimeric complex with TRMT112 to gain metabolic stability in cells. The crystal structure of METTL5-TRMT112 was solved at atomic resolution, revealing that its RNA-binding mode differs from other m6A methyltransferases, and suggesting an adenosine-extrusion mechanism analogous to a DNA methyltransferase. Biochemical identification of methyltransferase activity, crystal structure determination, cellular stability assays with TRMT112 complex Nucleic acids research High 31328227
2020 METTL5 catalyzes m6A modification of 18S rRNA at position A1832 in vivo and in vitro. Loss of Mettl5 in mouse embryonic stem cells decreases global translation rate, causes spontaneous loss of pluripotency, and compromises differentiation potential. In vitro methyltransferase assay, Mettl5 knockout mESCs with translation rate measurement and pluripotency/differentiation phenotyping Genes & development High 32217665
2020 METTL5 shows strong substrate preference for 18S rRNA 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. In vitro substrate specificity assays, polysome profiling, p70-S6K phosphorylation assays, structural comparison with yeast ribosome model Cell reports High 33357433
2020 Drosophila METTL5 ortholog CG9666 is required for specific deposition of m6A on 18S rRNA through direct interaction with the Drosophila TRMT112 ortholog CG12975. Loss of CG9666 depletes 18S rRNA m6A but does not compromise rRNA maturation; it instead impacts fly locomotor behavior. RNAi screen, m6A detection on 18S rRNA, direct interaction assay with Drosophila TRMT112 ortholog, behavioral assays EMBO reports High 32350990
2020 METTL5-mediated 18S rRNA m6A modification at A1832 is required for efficient translation of FBXW7 mRNA. Deficiency of METTL5 reduces FBXW7 protein levels and leads to accumulation of its substrate c-MYC, thereby delaying mESC differentiation. Mettl5 knockout mESCs, FBXW7 protein level measurement, c-MYC accumulation assay, differentiation rescue experiments EMBO reports High 32783360
2022 The METTL5-TRMT112 complex installs the m6A modification at position 1832 of human 18S rRNA. 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; Mettl5 knockout mice display reduced body size and metabolic defects. In vitro methyltransferase reconstitution with METTL5-TRMT112, interaction disruption by disease-associated mutants, translational profiling in KO cells and mice The Journal of biological chemistry High 35033535
2019 Bi-allelic frameshift variants in METTL5 cause autosomal-recessive intellectual disability and microcephaly. METTL5 protein is enriched in the nucleus and synapses of hippocampal neurons. Truncating variants alter METTL5 expression level but do not affect its subcellular localization in transfected cells and neurons. mettl5 knockdown in zebrafish recapitulates microcephaly. Exome sequencing with segregation analysis, subcellular localization by immunostaining in hippocampal neurons, zebrafish morpholino knockdown American journal of human genetics Medium 31564433
2020 Mettl5 knockout in mouse ESCs leads to abnormal craniofacial and nervous development. METTL5 protein complex was identified as primarily interacting with RNA-binding proteins and ribosome proteins. Mettl5 knockout mice exhibit intellectual disability. METTL5 maintains brain function by regulating the myelination process. Mettl5 KO mouse model, protein complex identification, behavioral testing, myelination analysis Genes & diseases Medium 35005123
2021 METTL5 promotes c-Myc translation specifically, as METTL5 overexpression-driven oncogenic effects in pancreatic cancer can be abolished by c-Myc knockdown. m6A modifications at the 5'UTR and CDS (near 5'UTR) of c-Myc mRNA play a critical role in this translation regulation. METTL5 and its cofactor TRMT112 synergistically promote pancreatic cancer progression. METTL5 overexpression/knockdown in pancreatic cancer cells, c-Myc rescue experiments, m6A site mapping on c-Myc mRNA, TRMT112 co-expression experiments International journal of oncology Medium 34970694
2022 Loss of METTL5 in cardiomyocytes promotes pressure overload-induced hypertrophy and adverse remodeling. METTL5 modulates the mRNA translation of SUZ12 (a core PRC2 complex component), and this translational regulation underlies the transcriptomic shifts during cardiac hypertrophy. Cardiac-specific METTL5 KO mouse model, gain- and loss-of-function in primary cardiomyocytes, SUZ12 translation assay Frontiers in cardiovascular medicine Medium 35295259
2022 METTL5 regulates cranial suture fusion by controlling osteogenic differentiation of suture mesenchymal stem cells. Mechanistically, Wnt signaling is significantly downregulated after Mettl5 knockout. Mettl5 KO mouse model, suture mesenchymal stem cell osteogenic differentiation assays, Wnt signaling pathway analysis Fundamental research Medium 38933773
2023 METTL5 upregulation promotes c-Myc stability in HCC by controlling USP5 translation. USP5 binds c-Myc via its c-Box and UBA domains and inhibits K48-linked polyubiquitination of c-Myc. CREB1/P300 was identified as a transcriptional regulator of METTL5 promoter activity. GST pulldown, coimmunoprecipitation, polysome profiling, luciferase reporter assays, RNA sequencing, non-targeted metabolomics, PDX mouse models Cancer communications Medium 36602428
2023 METTL5-mediated 18S rRNA m6A modification promotes translation of G-quadruplex-containing mRNAs enriched in the TGF-β pathway in intrahepatic cholangiocarcinoma. METTL5 depletion impairs ribosome synthesis and inhibits this selective translation. Loss- and gain-of-function assays in ICC cells, liver-specific KO and overexpression mouse models, translational profiling of G-quadruplex mRNAs Molecular therapy Medium 37735874
2024 METTL5 promotes ovarian cancer immune evasion by modulating ATF4 translation through alteration of 18S rRNA m6A levels. METTL5 KO disrupts ATF4 translation, leading to downregulation of SLC7A11 and SLC3A2, sensitizing tumors to T cell-mediated ferroptosis. The immune-sensitive phenotype of METTL5-KO tumors is reversed by ATF4 overexpression or ferroptosis inhibition. Genome-wide immune screens (in vitro and in vivo), METTL5 KO in ovarian cancer cells, ATF4 overexpression rescue experiments, ferroptosis inhibitor rescue Advanced science Medium 41042068
2024 METTL5 enhances UBE3C mRNA stability through m6A modification, enabling YTHDF1 to bind and protect modified UBE3C mRNA from degradation. UBE3C in turn promotes ubiquitination and degradation of AHNAK, suppressing ferroptosis in osteosarcoma cells. This defines a METTL5-YTHDF1-UBE3C-AHNAK axis. m6A modification assay on UBE3C mRNA, YTHDF1 binding assay, mRNA stability assay, UBE3C KD and AHNAK interaction experiments, ferroptosis assays Journal of molecular histology Low 40696164
2024 METTL5 upregulation promotes NRF2 mRNA stability through m6A modification, and m6A reader IGF2BP1 mediates NRF2 mRNA stability via the METTL5/m6A/NRF2 axis, thereby inactivating ferroptosis in gastric cancer. METTL5 KD/OE in gastric cancer cells, NRF2 mRNA stability assay, IGF2BP1 interaction assay, ferroptosis assays with iron measurement Cell death discovery Low 39261486
2024 METTL5 positively regulates TPRKB expression by enhancing TPRKB mRNA stability through m6A modification. METTL5 KD in HCC cells, TPRKB mRNA stability assay, m6A modification measurement, functional rescue experiments Experimental cell research Low 39182664
2024 METTL5-mediated 18S rRNA m6A modification promotes translation efficiency of cofilin-encoding Cfl1 and Inpp5k mRNAs in corticospinal neurons. Increased cofilin expression and activity stimulates actin polymerization, facilitating axon outgrowth and corticospinal tract sprouting after unilateral traumatic brain injury. METTL5 overexpression in corticospinal neurons, translation efficiency profiling, CST sprouting assay after TBI, cofilin expression and activity measurement Experimental neurology Medium 39406306
2025 METTL5-mediated 18S rRNA m6A modification promotes translation of SEPHS2, a selenophosphate synthetase. METTL5 depletion reduces SEPHS2 translation efficiency, leading to diminished selenoprotein synthesis and increased ROS, inducing apoptosis in multiple myeloma. Salvianolic acid C (SAC) was identified as a potential METTL5 inhibitor. METTL5 KD in MM cells and xenograft model, SEPHS2 translation efficiency measurement, ROS assay, SAC inhibitor treatment in vitro and in vivo Cell death & disease Medium 40750759
2025 METTL5 depletion in intrahepatic cholangiocarcinoma downregulates mRNA translation of CXCL16, reducing CD8+ T cell recruitment. METTL5-mediated 18S rRNA m6A modification controls immune microenvironment by selective translational regulation of chemokine mRNA. Liver-specific Mettl5 cKO mouse, scRNA-seq and scTCR-seq analysis, CXCL16 translational assay, adoptive macrophage transfer experiments, lipid nanoparticle siRNA delivery Advanced science Medium 41431992
2025 TRIM28 induces Mettl5 protein ubiquitination and degradation in airway CD4+ T cells. Reduced Mettl5 levels lead to hypomethylation of the Gata3 promoter and increased Gata3 transcription, promoting Th2 polarization. Inhibition of TRIM28 restores Mettl5 activity and Gata3 gene regulation. Chromatin immunoprecipitation, ELISA, TRIM28 interaction assay with Mettl5, ubiquitination assay, Mettl5-deficient CD4+ T cell mouse model Frontiers in immunology Medium 40391221
2025 Mettl5 in Drosophila functions within neurons and glia to regulate sleep by controlling PERIOD protein levels. Mettl5 forms a complex with Trmt112 to influence rRNA methylation; Trmt112 mutation recapitulates sleep disturbances. Loss of Mettl5 alters proteasome component expression and clock gene expression, resulting in net increased PERIOD protein that underlies the sleep phenotype. Drosophila Mettl5 genetic mutants, neuron/glia-specific rescue experiments, RNA-seq and Ribo-seq, PERIOD protein level measurement, genetic rescue with Trmt112 mutation eLife Medium 42100920
2025 METTL5 deficiency in mice causes male infertility with oligoasthenoteratozoospermia (OAT). Despite no notable change in global translation, METTL5 loss specifically decreases translation efficiency of spermiogenesis-related mRNAs including Gk2, Akap4, Fsip2, Odf2, and Pgk2. Mettl5 KO mouse model, sperm phenotyping, translation efficiency profiling by ribosome profiling, clinical variant identification in infertility patients Molecular therapy Medium 40783785
2026 Bicyclopyrrolidine acrylamide stereoprobes react with C100 of TRMT112 exclusively when TRMT112 is complexed with METTL5 (but not other methyltransferases). Co-crystal structure reveals that stereoprobe binding occurs at a composite pocket templated by both TRMT112-C100 and METTL5, absent in other TRMT112:MT complexes. Stereoprobe binding causes structural rearrangements that allosterically agonize METTL5 activity. Chemical proteomics (stereoprobe reactivity profiling), co-crystal structure of TRMT112-METTL5 with stereoprobe, in vitro methyltransferase activity assay Nature chemical biology High 41507545
2025 METTL5 deficiency impairs osteogenic differentiation by decreasing translation efficiency of OSER1 (oxidative stress-responsive serine-rich protein 1) mRNA, which downregulates antioxidant gene expression and diminishes antioxidant capacity. Administration of NAC (antioxidant) partially rescues skeletal defects in Mettl5-KO mice. Mettl5 KO mouse model, OSER1 translation efficiency measurement, antioxidant gene expression profiling, NAC rescue experiment JCI insight Medium 42100868
2026 Direct RNA sequencing (nanopore ONT) of Mettl5-KO versus WT mouse ESCs provides no compelling evidence for METTL5-mediated mRNA m6A methylation in vivo, indicating that METTL5 catalytic activity is restricted to rRNA and does not extend to mRNA. Direct RNA sequencing (nanopore ONT) with m6A detection, Mettl5-KO mESCs vs WT comparison, METTL3 inhibitor as positive control microPublication biology Medium 42181001
2025 METTL5-KO increases tumor neoantigen production by decreasing translation fidelity at the ribosomal decoding center. METTL5 deficiency leads to non-canonical translation products serving as neoantigens, increases CD8+ T cell infiltration and TCR diversity in murine tumors. This immunostimulatory effect depends on intact antigen presentation pathways. METTL5 KO in murine tumor models, neoantigen profiling, CD8+ T cell infiltration measurement, TCR repertoire sequencing, antigen presentation pathway dependency experiments bioRxivpreprint Low bio_10.1101_2025.06.06.658288
2025 In human cortical forebrain organoids, METTL5 knockout causes delay in neural stem cell proliferation and timing of neuronal differentiation. CHCHD2 (a mitochondrial gene) is significantly downregulated transcriptomically in METTL5-KO organoids, and overexpression of CHCHD2 rescues proliferation defects of METTL5-KO neural progenitor cells. METTL5 KO cortical forebrain organoids from iPSCs, transcriptomic analysis, CHCHD2 overexpression rescue experiment, proliferation assays bioRxivpreprint Low 40672170

Source papers

Stage 0 corpus · 55 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 430 31328227
2023 METTL5 stabilizes c-Myc by facilitating USP5 translation to reprogram glucose metabolism and promote hepatocellular carcinoma progression. Cancer communications (London, England) 145 36602428
2020 The rRNA m6A methyltransferase METTL5 is involved in pluripotency and developmental programs. Genes & development 125 32217665
2020 Ribosome 18S m6A Methyltransferase METTL5 Promotes Translation Initiation and Breast Cancer Cell Growth. Cell reports 125 33357433
2019 Bi-allelic Variants in METTL5 Cause Autosomal-Recessive Intellectual Disability and Microcephaly. American journal of human genetics 81 31564433
2020 The 18S rRNA m6 A methyltransferase METTL5 promotes mouse embryonic stem cell differentiation. EMBO reports 69 32783360
2020 The 18S ribosomal RNA m6 A methyltransferase Mettl5 is required for normal walking behavior in Drosophila. EMBO reports 65 32350990
2022 The METTL5-TRMT112 N6-methyladenosine methyltransferase complex regulates mRNA translation via 18S rRNA methylation. The Journal of biological chemistry 63 35033535
2021 Ribosome 18S m6A methyltransferase METTL5 promotes pancreatic cancer progression by modulating c‑Myc translation. International journal of oncology 50 34970694
2020 Mettl5 mediated 18S rRNA N6-methyladenosine (m6A) modification controls stem cell fate determination and neural function. Genes & diseases 43 35005123
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
2022 The emerging importance of METTL5-mediated ribosomal RNA methylation. Experimental & molecular medicine 38 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 22 39261486
2024 The m6A methyltransferase METTL5 promotes neutrophil extracellular trap network release to regulate hepatocellular carcinoma progression. Cancer medicine 14 38613157
2022 METTL5 regulates cranial suture fusion via Wnt signaling. Fundamental research 13 38933773
2024 METTL5 enhances the mRNA stability of TPRKB through m6A modification to facilitate the aggressive phenotypes of hepatocellular carcinoma cell. Experimental cell research 9 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
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 6 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 6 36305450
2025 Scutellarin suppresses ovarian cancer progression by targeting METTL5. Scientific reports 5 40425707
2025 METTL5 regulates SEPHS2-mediated selenoprotein synthesis to promote multiple myeloma survival and progression. Cell death & disease 5 40750759
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
2025 Tumor Intrinsic METTL5 Modulates ATF4 Translation to Prevent T Cell-Induced Ferroptosis in Ovarian Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 4 41042068
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
2024 METTL4 and METTL5 as biomarkers for recurrence-free survival in hepatocellular carcinoma patients. Future oncology (London, England) 4 39706798
2026 Complexoform-restricted covalent TRMT112 ligands that allosterically agonize METTL5. Nature chemical biology 3 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 3 39870169
2025 Microcephaly-related global developmental delay caused by a pathogenic METTL5 splicing mutation in a Chinese family. Journal of human genetics 3 40500307
2025 METTL5-mediated m6A modification of UBE3C promotes osteosarcoma progression by suppressing ferroptosis via inducing AHNAK ubiquitination. Journal of molecular histology 3 40696164
2024 Biological significance of METTL5 in atherosclerosis: comprehensive analysis of single-cell and bulk RNA sequencing data. Aging 3 38663914
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 Complexoform-restricted covalent TRMT112 ligands that allosterically agonize METTL5. bioRxiv : the preprint server for biology 2 40475643
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 2 40783785
2026 Heterozygous loss-of-function variant in METTL5 is associated with intellectual disability. Human molecular genetics 1 41873838
2025 TRIM28 mediates Mettl5 ubiquitination to promotes Th2 polarization. Frontiers in immunology 1 40391221
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 Enables Immune Evasion of Liver Cancer via Chemokine mRNA Translation Regulation. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 1 41431992
2025 Functional Interpretation of a Novel Homozygous METTL5 Variant Associated with ADHD and Neurodevelopmental Abnormalities: A Case Report and Literature Review. Genes 1 41465175
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 METTL5 reprograms glycolytic metabolism and promotes non-small cell lung cancer progression by modifying PGAM1. Oncology letters 0 42057886
2026 METTL5 deficiency impairs osteogenesis through OSER1-dependent antioxidant regulation. JCI insight 0 42100868
2026 Mettl5 coordinates protein production and degradation of PERIOD to regulate sleep in Drosophila. eLife 0 42100920
2026 Resolving METTL5 Specificity: Direct RNA Sequencing Reveals No Compelling Evidence for METTL5 mediated mRNA m6A Methylation in mESCs. microPublication biology 0 42181001
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 METTL5 in physiology and pathology: mechanisms and implications. Frontiers in cell and developmental biology 0 41487998

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