Affinage

METTL14

N(6)-adenosine-methyltransferase non-catalytic subunit METTL14 · UniProt Q9HCE5

Length
456 aa
Mass
52.1 kDa
Annotated
2026-04-28
100 papers in source corpus 34 papers cited in narrative 34 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

METTL14 is an essential scaffold subunit of the mammalian m6A methyltransferase complex, functioning as a catalytically inactive RNA-binding platform that heterodimerizes with the catalytic subunit METTL3 to deposit N6-methyladenosine on mRNA and other nuclear RNAs, thereby regulating mRNA stability, translation, and pri-miRNA processing across diverse physiological contexts including hematopoiesis, β-cell function, adipocyte metabolism, and immune responses (PMID:24316715, PMID:27281194, PMID:29348140, PMID:31029827, PMID:37526326). Structurally, METTL14 contributes a positively charged RNA-binding groove and C-terminal RGG repeats that engage RNA substrates—including G-quadruplex structures—while METTL3 exclusively harbors the S-adenosylmethionine-binding catalytic pocket (PMID:27281194, PMID:29348140, PMID:34908152). METTL14 protein stability and activity are regulated by PRMT1/PRMT3-mediated arginine methylation, p38-dependent phosphorylation at Thr72 that promotes liquid–liquid phase separation, and ubiquitin-proteasomal degradation mediated by HRD1 and STUB1, the latter competitively blocked by METTL3 binding (PMID:34145242, PMID:37269817, PMID:34847358, PMID:36597993, PMID:38548762). Independently of METTL3 and m6A catalysis, METTL14 localizes to chromatin where it binds H3K27me3 at bivalent domains and recruits the demethylase KDM6B and PRC2 to maintain bivalent chromatin integrity during embryonic stem cell differentiation (PMID:33795874, PMID:37314930, PMID:37030005).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2013 High

    Establishing METTL14 as a core m6A methyltransferase subunit resolved the long-standing question of which proteins catalyze m6A in mammalian cells, revealing a METTL3–METTL14 heterodimeric writer complex that interacts with WTAP.

    Evidence Biochemical reconstitution, Co-IP, and in vitro methylation assays in mammalian cells

    PMID:24316715

    Open questions at the time
    • Relative catalytic contributions of METTL3 versus METTL14 were not resolved
    • Structural basis of the heterodimer was unknown
    • Mechanism of substrate RNA selection was undefined
  2. 2016 High

    High-resolution crystal structures revealed that METTL3 alone contains the AdoMet-binding catalytic pocket while METTL14 serves as a structurally degenerate, catalytically inactive scaffold providing the RNA-binding platform, resolving the division of labor within the complex.

    Evidence X-ray crystallography at 1.6–1.9 Å resolution with biochemical binding studies

    PMID:27281194

    Open questions at the time
    • How METTL14's RNA-binding surface selects specific substrates was unclear
    • Post-translational regulation of the complex was unknown
  3. 2018 High

    Demonstration that METTL14's C-terminal RGG repeats are essential for RNA binding and complex activity established the molecular basis for METTL14's obligate contribution to catalysis despite lacking intrinsic methyltransferase activity.

    Evidence In vitro methylation with recombinant proteins, mutagenesis of RGG repeats, phosphoproteomics

    PMID:29348140

    Open questions at the time
    • Whether RGG repeats recognize specific RNA structures was untested
    • Functional significance of identified phosphorylation sites was not established
  4. 2017 High

    Identification of MYB/MYC mRNAs as direct m6A targets downstream of METTL14 in AML, regulated by SPI1 transcriptional control of METTL14, demonstrated pathological consequences of METTL14-mediated m6A and established a disease-relevant signaling axis.

    Evidence Silencing/overexpression in AML cells and mouse models, MeRIP-seq, RNA stability assays

    PMID:29290617

    Open questions at the time
    • How m6A readers decode MYB/MYC transcripts downstream was not defined
    • Whether METTL14 has AML-independent oncogenic roles was unclear
  5. 2019 High

    Conditional β-cell knockout demonstrated a physiological requirement for METTL14-mediated m6A in insulin secretion and β-cell survival, linking epitranscriptomic regulation to glucose homeostasis in vivo.

    Evidence β-cell-specific Mettl14 KO mice (RIP-Cre), glucose tolerance tests, TUNEL, RNA-seq

    PMID:31029827

    Open questions at the time
    • Specific m6A target transcripts responsible for β-cell phenotype were not identified
    • Contribution of METTL14's m6A-independent chromatin roles in β-cells was not addressed
  6. 2021 High

    Discovery that METTL14 binds H3K27me3 and recruits KDM6B to regulate chromatin independently of METTL3 and m6A catalysis established a fundamentally new, m6A-independent chromatin-regulatory function for METTL14 in stem cell differentiation.

    Evidence ChIP-seq, METTL14 KO mESCs, enzymatic-dead mutant rescue, Co-IP with KDM6B

    PMID:33795874

    Open questions at the time
    • Structural basis of METTL14–H3K27me3 interaction was unknown
    • Whether this chromatin role operates in differentiated somatic tissues was untested
  7. 2021 High

    PRMT1-mediated arginine methylation at R255 was shown to enhance METTL14's interaction with WTAP and RNA substrates, revealing the first post-translational regulatory mechanism that tunes m6A writer complex activity.

    Evidence Mass spectrometry, R255K mutant mESCs, reciprocal Co-IP, in vitro methylation, MeRIP-seq

    PMID:34145242

    Open questions at the time
    • Whether other PRMTs contribute additional arginine methylation events was not resolved
    • Downstream reader recognition of PRMT1-regulated m6A sites was not examined
  8. 2021 High

    HRD1-mediated ubiquitination and proteasomal degradation of METTL14 under basal conditions, relieved during ER stress, established ubiquitin-dependent protein turnover as a mechanism linking ER proteostasis to m6A homeostasis and CHOP mRNA decay.

    Evidence Co-IP, ubiquitination assays, liver-specific KO mice, MeRIP-seq, m6A site mutagenesis

    PMID:34847358

    Open questions at the time
    • Whether other E3 ligases contribute to METTL14 turnover under different stress conditions was unexplored
  9. 2021 High

    METTL14-mediated m6A on EBI3 mRNA in tumor-associated macrophages was shown to suppress CD8+ T cell function, establishing METTL14 as a regulator of anti-tumor immunity through epitranscriptomic control of cytokine expression.

    Evidence Macrophage-specific Mettl14 KO mice, MeRIP, EBI3 neutralization, T cell functional assays

    PMID:34019807

    Open questions at the time
    • Whether METTL14 affects other immune checkpoint pathways beyond EBI3 was not addressed
    • Therapeutic targetability of METTL14 in immune cells was not tested
  10. 2022 Medium

    The METTL14 RGG domain was found to bind RNA G-quadruplex structures, providing a structural basis for how the m6A writer complex is recruited to specific methylation sites near rG4-forming sequences.

    Evidence EMSA, in vitro methylation assays, RGG deletion/mutation analysis

    PMID:34908152

    Open questions at the time
    • In vivo validation of rG4-dependent m6A targeting was lacking
    • Whether rG4 binding accounts for a major fraction of METTL14-dependent m6A sites was unknown
  11. 2023 High

    STUB1-mediated ubiquitination at K148/K156/K162 and competitive protection by METTL3 binding revealed a homeostatic feedback mechanism ensuring that free METTL14 is rapidly degraded while complexed METTL14 is stabilized.

    Evidence Co-IP, ubiquitination assays, METTL3 deletion constructs, dot blot m6A quantification

    PMID:36597993

    Open questions at the time
    • Whether STUB1 and HRD1 act redundantly or in distinct compartments was not clarified
    • Structural basis of METTL3–STUB1 competition for METTL14 was not resolved
  12. 2023 High

    Extension of METTL14's chromatin role showed it recruits not only KDM6B but also PRC2 and KDM5B to bivalent domains, maintaining both H3K27me3 and H3K4me3 marks, refining the model of how METTL14 preserves bivalent chromatin independently of m6A.

    Evidence ChIP-seq, METTL14 KO mESCs, Co-IP with PRC2 and KDM5B, nascent RNA assays

    PMID:37030005 PMID:37314930

    Open questions at the time
    • Whether METTL14's chromatin function operates in differentiated cell types beyond mESCs was unknown
    • How METTL14 simultaneously recruits antagonistic enzymes (KDM6B vs PRC2) to the same loci was not mechanistically resolved
  13. 2024 Medium

    p38 MAPK-mediated phosphorylation of METTL14 at Thr72 was shown to promote its liquid–liquid phase separation and interaction with METTL3, revealing a new regulatory layer connecting inflammatory signaling to m6A complex assembly.

    Evidence Phosphorylation assays, LLPS experiments, T72A mutant, MeRIP, in vivo M. tuberculosis infection models

    PMID:38548762

    Open questions at the time
    • Whether LLPS of METTL14 is a general regulatory mechanism beyond mycobacterial infection is untested
    • Structural determinants of phosphorylation-driven phase separation are unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How METTL14 coordinates its dual functions as an m6A writer subunit and an m6A-independent chromatin regulator within the same cell, and whether these functions are mutually exclusive or spatiotemporally segregated, remains unresolved.
  • No structural model of METTL14 bound to H3K27me3 nucleosomes exists
  • Whether post-translational modifications differentially direct METTL14 to RNA versus chromatin functions is unknown
  • The relative contribution of m6A-dependent versus m6A-independent METTL14 functions in disease contexts has not been systematically dissected

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 3 GO:0005198 structural molecule activity 3 GO:0042393 histone binding 3 GO:0016740 transferase activity 2
Localization
GO:0005634 nucleus 3 GO:0005694 chromosome 3
Pathway
R-HSA-8953854 Metabolism of RNA 4 GO:0005694 chromosome 3 R-HSA-168256 Immune System 3 R-HSA-4839726 Chromatin organization 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
HRD1KDM5BKDM6BMETTL3PRC2PRMT1STUB1WTAP
Complex memberships
METTL3–METTL14 m6A methyltransferase complexMETTL3–METTL14–WTAP writer complex

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 METTL14 catalyzes N6-methyladenosine (m6A) RNA methylation and forms a stable heterodimer core complex with METTL3 that functions in cellular m6A deposition on mammalian nuclear RNAs; WTAP interacts with this complex and affects methylation. Biochemical characterization, Co-IP, in vitro methylation assay Nature chemical biology High 24316715
2016 Crystal structures of METTL3-METTL14 heterodimer reveal that METTL3 is the catalytic core (AdoMet binds only to METTL3 pocket), while METTL14 serves as an RNA-binding platform with a positively charged groove; combined biochemical analysis confirms this division of labor. X-ray crystallography (1.6-1.9 Å resolution), biochemical assays, ligand-binding studies Nature High 27281194
2018 The C-terminal RGG repeats of METTL14 are required for METTL3/METTL14 methyltransferase activity by contributing to RNA substrate binding; monomeric METTL3 is soluble but inactive, and METTL14 alone has a degenerated catalytic center and is also inactive. Nuclear localization signals were identified and endogenous phosphorylation sites were mapped on both proteins. In vitro methylation assay with recombinant proteins, binding surface mapping, mutagenesis, mass spectrometry phosphoproteomics RNA (New York, N.Y.) High 29348140
2021 METTL14 binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independently of METTL3 and independently of m6A methyltransferase activity, regulating heterochromatin and the transition from self-renewal to differentiation in mouse embryonic stem cells. ChIP-seq, KO mESCs, co-IP, functional differentiation assays Nature cell biology High 33795874
2021 PRMT1 interacts with METTL14 and methylates it at arginine 255 (R255me), which greatly enhances interaction of METTL3/METTL14 with WTAP and promotes binding of the complex to substrate RNA, thereby increasing global mRNA m6A modification and driving endoderm differentiation in mESCs. Mass spectrometry, reciprocal Co-IP, in vitro methylation, METTL14 R255K mutant mESCs, MeRIP-seq Nature communications High 34145242
2021 HRD1 E3 ligase mediates ubiquitination and degradation of METTL14 under basal ER conditions; accumulation of unfolded/misfolded proteins during ER stress competes with HRD1-ERAD to block METTL14 ubiquitination, stabilizing METTL14 which then promotes m6A-dependent decay of CHOP mRNA (via its 3'UTR m6A) to suppress pro-apoptotic signaling. Co-IP, ubiquitination assay, liver-specific KO mice, MeRIP-seq, mutagenesis of m6A sites, luciferase reporter Molecular cell High 34847358
2023 STUB1 E3 ligase directly interacts with METTL14 and mediates its ubiquitination at lysines K148, K156, and K162, leading to proteasomal degradation and decreased global m6A; METTL3 competes with STUB1 for METTL14 binding (via METTL3 residues 450-454 and 464-480), thereby protecting METTL14 from degradation and maintaining m6A homeostasis. Co-IP, ubiquitination assay, mutagenesis, METTL3 deletion constructs, dot blot EMBO reports High 36597993
2023 METTL14 specifically binds bivalent chromatin domains (H3K27me3/H3K4me3) and recruits PRC2 (H3K27 methyltransferase) and KDM5B (H3K4 demethylase) to chromatin, independently of METTL3 or m6A, to enhance H3K27me3 and reduce H3K4me3, thereby maintaining bivalent domain integrity in mESCs. ChIP-seq, METTL14 KO mESCs, Co-IP with PRC2 and KDM5B, nascent RNA assays Cell reports High 37314930
2023 METTL14 binds H3K27me3 and recruits KDM6B to demethylate H3K27me3 independently of its RNA methyltransferase activity; depletion of METTL14 causes global H3K27me3 increase and gene suppression, establishing a chromatin regulatory role distinct from METTL3. ChIP-seq, KO mESCs, Co-IP, enzymatic mutant rescue experiments Protein & cell High 37030005
2022 METTL14 RGG repeats bind RNA G-quadruplex (rG4) structures, and the METTL3/METTL14 heterodimer selectively methylates adenosines close to rG4 sequences, suggesting direct recruitment of the m6A writer complex to specific methylation sites near G4-forming regions. Electrophoretic mobility shift assay, in vitro methylation assay, deletion/mutation analysis of RGG repeats Nucleic acids research Medium 34908152
2021 METTL3-METTL14 complex is active in vitro on double-stranded DNA containing UV-induced cyclopyrimidine dimers, abasic sites, or mismatches, producing N6-methyladenine (N6mA) in DNA; N6mA in the template strand inhibits its excision by the adenine DNA glycosylase MYH, suggesting a mechanism for reducing inappropriate misrepair at DNA lesion sites. In vitro methylation assay on DNA substrates, structural analysis of YTHDC1 with gapped DNA duplex Nucleic acids research Medium 34086966
2022 RNA binding to METTL3-METTL14 restricts N6-deoxyadenosine methylation of DNA in vitro; the complex preferentially catalyzes m6dA in single-stranded DNA despite weaker DNA binding, while it binds structured RNAs with high affinity but methylates them less efficiently than ssDNA. Systematic in vitro methylation activity assays and binding affinity measurements with various DNA/RNA substrates eLife Medium 35060905
2021 METTL14 promotes global genome repair (GGR) through m6A-mediated translation of DDB2 mRNA; UVB irradiation degrades METTL14 via NBR1-dependent selective autophagy; overexpression of enzymatically active (but not inactive mutant) METTL14 restores GGR and DDB2 levels; YTHDF1 (m6A reader) also binds DDB2 transcript and promotes its translation. KD/OE with enzymatic mutant, autophagy assay, GGR assay, Co-IP/RIP, mouse skin KO model PNAS High 34452996
2017 METTL14 regulates MYB and MYC mRNA targets through m6A modification to exert its oncogenic role in AML; the protein is negatively regulated at the transcriptional level by SPI1, defining a SPI1-METTL14-MYB/MYC signaling axis in myelopoiesis. Silencing/overexpression in AML cells and mouse models, MeRIP-seq, RNA stability assays, ChIP for SPI1 Cell stem cell High 29290617
2021 METTL14 increases m6A modification of FOXO1 mRNA and enhances its translation through YTHDF1 recognition; METTL14 also directly binds to FOXO1 protein and acts on the promoters of VCAM-1 and ICAM-1 to promote their transcription, mediating endothelial cell inflammatory response and atherosclerotic plaque formation. RIP assay, MeRIP-seq, METTL14 KO mice, Co-IP, luciferase reporter Theranostics Medium 32802173
2022 METTL14 increases m6A modification of Myd88 mRNA to stabilize it, activating the MyD88/NF-κB/IL-6 pathway in macrophages; Myd88 then affects p65 nuclear distribution to regulate IL-6 transcription, promoting macrophage inflammation and atherosclerosis. MeRIP, RIP, mRNA stability assay, Mettl14 KO mice, NF-κB reporter Cellular and molecular life sciences Medium 35598196
2021 Macrophage-specific Mettl14 knockout decreases m6A on Ebi3 mRNA and increases EBI3 (cytokine subunit) transcript levels, driving CD8+ T cell dysfunction; neutralization of EBI3 reinvigorates dysfunctional CD8+ T cells, placing METTL14-mediated m6A upstream of EBI3 in tumor immune suppression. Macrophage-specific KO mice, MeRIP, mRNA stability, EBI3 neutralization, T cell functional assays Cancer cell High 34019807
2021 Viral EBV oncoprotein EBNA3C activates transcription of METTL14 and directly interacts with METTL14 to promote its protein stability, thereby hijacking METTL14-mediated m6A modification of viral latent transcripts to drive EBV-associated tumorigenesis. Co-IP, Co-immunofluorescence, knockdown, xenograft tumor models PLoS pathogens Medium 31226160
2020 METTL14 regulates m6A modification of pri-miR-19a, enhancing its processing to mature miR-19a through recognition by the microprocessor component DGCR8 in a METTL14-dependent manner, thereby promoting proliferation and invasion of atherosclerotic vascular endothelial cells. Co-IP (METTL14-DGCR8), RIP, RT-qPCR, KD/OE experiments European review for medical and pharmacological sciences Medium 32633395
2021 PRMT1 methylates METTL14 at two major arginine residues at its C-terminus; the reader protein SPF30 recognizes this asymmetric dimethylarginine modification; arginine methylation of METTL14 is required for its function in catalyzing m6A modification. Co-IP, in vitro methylation, PRMT1 inhibitor treatment, mass spectrometry Neoplasia (New York, N.Y.) Medium 37269817
2023 PRMT3 interacts with METTL14 and mediates its arginine methylation; PRMT3 inhibition leads to METTL14 overexpression which promotes m6A modification via YTHDF2-dependent mechanism, reducing GPX4 mRNA stability and accelerating ferroptosis in endometrial cancer cells. Co-IP, in vitro arginine methylation, MeRIP, YTHDF2 RIP, xenograft models Advanced science Medium 37973560
2024 M. tuberculosis-secreted EsxB interacts with p38 MAP kinase to inhibit TAB1-mediated p38 autophosphorylation, which in turn prevents p38-mediated phosphorylation of METTL14 at Thr72, inhibiting liquid-liquid phase separation (LLPS) of METTL14 and its interaction with METTL3, resulting in decreased m6A modification of Nox2 mRNA and reduced host ROS-mediated anti-TB immunity. Co-IP, phosphorylation assays, LLPS experiments, MeRIP, METTL14 Thr72 mutation, in vivo infection models Cell discovery Medium 38548762
2021 LNC942 (LINC00942) directly recruits METTL14 protein via a specific sequence (+176-+265), stabilizing METTL14-mediated m6A methylation and increasing mRNA stability and protein expression of downstream targets CXCR4 and CYP1B1 in breast cancer cells. RNA pulldown, RIP, MeRIP, Co-IP, deletion mapping, in vivo xenograft Oncogene Medium 32576970
2019 β-cell-specific deletion of Mettl14 in mice causes glucose intolerance due to reduced insulin secretion, increased β-cell death, and decreased β-cell mass; RNA-seq revealed upregulation of IRE1α/sXBP-1 ER stress pathway, suggesting METTL14-mediated m6A is required for β-cell survival and function. Conditional KO mice (RIP-Cre), glucose tolerance tests, GSIS, TUNEL, RNA-seq Biochimica et biophysica acta. Molecular basis of disease High 31029827
2022 METTL14 mediates m6A modification of METTL14 promotes maturation of pri-miR-17 by inhibiting YTHDC2-mediated recognition of the 'GGACC' binding site, thereby preventing pri-miR-17 mRNA decay and reducing mature miR-17-5p levels, which in turn affects Mitofusin 2 (MFN2) and mitochondrial homeostasis in colorectal cancer. MeRIP-seq, RIP, RNA stability assays, miRNA overexpression/knockdown Cell death & disease Medium 36810285
2023 The METTL14 R298P cancer-associated mutation reduces m6A modification at canonical motifs but induces m6A modification at aberrant motifs; aberrant methylation alters methylation efficiency at surrounding canonical sites, including c-MET mRNA, severely destabilizing it, reducing c-Myc expression, and suppressing cell proliferation. MeRIP-seq in isogenic cell lines with heterozygous/homozygous R298P mutation, mRNA stability assays Cell reports Medium 37355987
2021 METTL14 promotes m6A modification of Notch1 mRNA, inhibiting its RNA stability and thus reducing Notch1 expression to suppress bladder tumor-initiating cell self-renewal and tumorigenesis. KO/overexpression, MeRIP, mRNA stability assay, in vivo tumorigenesis assay Molecular cancer Medium 31760940
2024 Cardiac METTL14 silencing suppresses Phlpp2 mRNA m6A modifications and activates Akt-S473 signaling to regulate cardiomyocyte growth and apoptosis; overexpression of wild-type but not MTase-inactive mutant METTL14 blocks exercise-induced physiological cardiac hypertrophy. Cardiac-specific KD and OE in vivo, enzymatic mutant, MeRIP, Akt signaling assays Nature communications High 36351918
2023 METTL14 promotes m6A modification of KAT3B mRNA to enhance its expression; KAT3B then increases STING expression by enhancing H3K27ac at the STING promoter; this METTL14-KAT3B-STING axis promotes M1 macrophage polarization and NLRP3 inflammasome/pyroptosis after ischemic stroke. METTL14 knockdown in rats and cells, MeRIP, ChIP, in vivo MCAO model Neurobiology of disease Medium 37541353
2024 METTL14 mediates m6A modification of GluN2A (NMDAR subunit) mRNA via IGF2BP2 to stabilize it, enhancing presynaptic NMDAR activity in DRG neurons and contributing to chemotherapy-induced neuropathic pain; DBP transcription factor regulates METTL14 expression in this context. MeRIP, RIP, gain/loss-of-function in vivo and in vitro, behavioral pain assays, immunofluorescence in human DRGs The Journal of clinical investigation Medium 38319733
2021 NF-κB directly transactivates METTL14 (and METTL3) gene promoters upon LPS challenge in Kupffer cells; METTL14-mediated m6A on the 5'UTR of TGF-β1 mRNA promotes its cap-independent translation; METTL14 KO in myeloid cells abolishes LPS-induced TGF-β1 upregulation. ChIP-PCR, dual-luciferase reporter, m6A-seq, METTL14 KO mice, MeRIP with 5'UTR mutation Cellular and molecular gastroenterology and hepatology High 33992834
2017 METTL3 and METTL14 cooperate in m6A modification to enhance translation of p21 3'UTR: METTL3/METTL14-mediated m6A facilitates NSUN2-mediated m5C methylation and vice versa; both modifications synergistically enhance p21 protein expression at the translational level during oxidative stress-induced senescence. In vitro methylation assays, KD of individual writers, p21 translation reporter assays Journal of cellular biochemistry Medium 28247949
2022 METTL14-mediated m6A modification of NLRP3 mRNA is recognized by IGF2BP2 which stabilizes NLRP3 mRNA, activating the NLRP3 inflammasome in macrophages during acute lung injury; knockdown of IGF2BP2 diminished LPS-induced ALI in mice. MeRIP, RIP, IGF2BP2 KD, mouse ALI models Cell death & disease Medium 38218935
2023 Adipose METTL14 installs m6A on Adrb2, Adrb3, Atgl, and Cgi-58 transcripts in adipocytes, suppressing their translation; adipocyte-specific Mettl14 deletion decreases m6A on these transcripts and increases protein levels, thereby enhancing β-adrenergic signaling and lipolysis and protecting mice from diet-induced obesity. Adipocyte-specific Mettl14 KO mice, MeRIP, polysome profiling, metabolic phenotyping Advanced science High 37526326

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation. Nature chemical biology 2733 24316715
2016 Structural basis of N(6)-adenosine methylation by the METTL3-METTL14 complex. Nature 980 27281194
2017 METTL14 Inhibits Hematopoietic Stem/Progenitor Differentiation and Promotes Leukemogenesis via mRNA m6A Modification. Cell stem cell 822 29290617
2020 METTL14 suppresses proliferation and metastasis of colorectal cancer by down-regulating oncogenic long non-coding RNA XIST. Molecular cancer 436 32111213
2017 Mettl3-/Mettl14-mediated mRNA N6-methyladenosine modulates murine spermatogenesis. Cell research 406 28914256
2018 Interactions, localization, and phosphorylation of the m6A generating METTL3-METTL14-WTAP complex. RNA (New York, N.Y.) 376 29348140
2020 METTL14-mediated N6-methyladenosine modification of SOX4 mRNA inhibits tumor metastasis in colorectal cancer. Molecular cancer 324 32552762
2017 NSUN2-Mediated m5C Methylation and METTL3/METTL14-Mediated m6A Methylation Cooperatively Enhance p21 Translation. Journal of cellular biochemistry 233 28247949
2021 The loss of RNA N6-adenosine methyltransferase Mettl14 in tumor-associated macrophages promotes CD8+ T cell dysfunction and tumor growth. Cancer cell 226 34019807
2020 METTL14 aggravates endothelial inflammation and atherosclerosis by increasing FOXO1 N6-methyladeosine modifications. Theranostics 224 32802173
2020 LNC942 promoting METTL14-mediated m6A methylation in breast cancer cell proliferation and progression. Oncogene 173 32576970
2021 METTL14-regulated PI3K/Akt signaling pathway via PTEN affects HDAC5-mediated epithelial-mesenchymal transition of renal tubular cells in diabetic kidney disease. Cell death & disease 167 33414476
2022 METTL14 suppresses pyroptosis and diabetic cardiomyopathy by downregulating TINCR lncRNA. Cell death & disease 160 35013106
2022 Mettl14 mediates the inflammatory response of macrophages in atherosclerosis through the NF-κB/IL-6 signaling pathway. Cellular and molecular life sciences : CMLS 158 35598196
2019 Mettl14 inhibits bladder TIC self-renewal and bladder tumorigenesis through N6-methyladenosine of Notch1. Molecular cancer 157 31760940
2021 m6A-independent genome-wide METTL3 and METTL14 redistribution drives the senescence-associated secretory phenotype. Nature cell biology 139 33795874
2018 The RNA Methyltransferase Complex of WTAP, METTL3, and METTL14 Regulates Mitotic Clonal Expansion in Adipogenesis. Molecular and cellular biology 132 29866655
2021 The RNA m6A writer METTL14 in cancers: Roles, structures, and applications. Biochimica et biophysica acta. Reviews on cancer 125 34375716
2022 Functions, mechanisms, and therapeutic implications of METTL14 in human cancer. Journal of hematology & oncology 124 35115038
2021 METTL14 aggravates podocyte injury and glomerulopathy progression through N6-methyladenosine-dependent downregulating of Sirt1. Cell death & disease 107 34580283
2021 Downregulated METTL14 accumulates BPTF that reinforces super-enhancers and distal lung metastasis via glycolytic reprogramming in renal cell carcinoma. Theranostics 102 33664855
2020 METTL14 regulates M6A methylation-modified primary miR-19a to promote cardiovascular endothelial cell proliferation and invasion. European review for medical and pharmacological sciences 102 32633395
2019 EBV epitranscriptome reprogramming by METTL14 is critical for viral-associated tumorigenesis. PLoS pathogens 102 31226160
2022 METTL14 is required for exercise-induced cardiac hypertrophy and protects against myocardial ischemia-reperfusion injury. Nature communications 101 36351918
2021 METTL14 promotes glomerular endothelial cell injury and diabetic nephropathy via m6A modification of α-klotho. Molecular medicine (Cambridge, Mass.) 95 34503454
2021 METTL14 facilitates global genome repair and suppresses skin tumorigenesis. Proceedings of the National Academy of Sciences of the United States of America 92 34452996
2022 N6-methyladenosine-modified TRAF1 promotes sunitinib resistance by regulating apoptosis and angiogenesis in a METTL14-dependent manner in renal cell carcinoma. Molecular cancer 90 35538475
2022 piRNA-14633 promotes cervical cancer cell malignancy in a METTL14-dependent m6A RNA methylation manner. Journal of translational medicine 81 35093098
2020 Downregulation of METTL14 increases apoptosis and autophagy induced by cisplatin in pancreatic cancer cells. The international journal of biochemistry & cell biology 80 32097728
2023 METTL14 regulates microglia/macrophage polarization and NLRP3 inflammasome activation after ischemic stroke by the KAT3B-STING axis. Neurobiology of disease 79 37541353
2021 METTL3/METTL14 Transactivation and m6A-Dependent TGF-β1 Translation in Activated Kupffer Cells. Cellular and molecular gastroenterology and hepatology 79 33992834
2019 METTL14 is essential for β-cell survival and insulin secretion. Biochimica et biophysica acta. Molecular basis of disease 71 31029827
2023 METTL14 is a chromatin regulator independent of its RNA N6-methyladenosine methyltransferase activity. Protein & cell 69 37030005
2022 Downregulation of METTL14 improves postmenopausal osteoporosis via IGF2BP1 dependent posttranscriptional silencing of SMAD1. Cell death & disease 69 36319624
2020 The study of METTL14, ALKBH5, and YTHDF2 in peripheral blood mononuclear cells from systemic lupus erythematosus. Molecular genetics & genomic medicine 68 32583611
2021 Arginine methylation of METTL14 promotes RNA N6-methyladenosine modification and endoderm differentiation of mouse embryonic stem cells. Nature communications 65 34145242
2021 HRD1-mediated METTL14 degradation regulates m6A mRNA modification to suppress ER proteotoxic liver disease. Molecular cell 65 34847358
2022 METTL14-mediated epitranscriptome modification of MN1 mRNA promote tumorigenicity and all-trans-retinoic acid resistance in osteosarcoma. EBioMedicine 64 35810559
2023 PRMT3-Mediated Arginine Methylation of METTL14 Promotes Malignant Progression and Treatment Resistance in Endometrial Carcinoma. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 61 37973560
2020 Analysis of METTL3 and METTL14 in hepatocellular carcinoma. Aging 57 33159022
2021 Human MettL3-MettL14 RNA adenine methyltransferase complex is active on double-stranded DNA containing lesions. Nucleic acids research 55 34086966
2022 The role, mechanism, and application of RNA methyltransferase METTL14 in gastrointestinal cancer. Molecular cancer 51 35974338
2021 METTL14-mediated Lnc-LSG1 m6A modification inhibits clear cell renal cell carcinoma metastasis via regulating ESRP2 ubiquitination. Molecular therapy. Nucleic acids 51 35036065
2024 Discovery of a PROTAC degrader for METTL3-METTL14 complex. Cell chemical biology 50 38194973
2021 Isorhapontigenin (ISO) inhibits EMT through FOXO3A/METTL14/VIMENTIN pathway in bladder cancer cells. Cancer letters 50 34332039
2022 The m6A RNA methyltransferase METTL3/METTL14 promotes leukemogenesis through the mdm2/p53 pathway in acute myeloid leukemia. Journal of Cancer 48 35154467
2023 METTL14-dependent maturation of pri-miR-17 regulates mitochondrial homeostasis and induces chemoresistance in colorectal cancer. Cell death & disease 46 36810285
2024 A Stapled Peptide Inhibitor Targeting the Binding Interface of N6-Adenosine-Methyltransferase Subunits METTL3 and METTL14 for Cancer Therapy. Angewandte Chemie (International ed. in English) 44 38607929
2022 Recognition of G-quadruplex RNA by a crucial RNA methyltransferase component, METTL14. Nucleic acids research 43 34908152
2021 Insights into roles of METTL14 in tumors. Cell proliferation 42 34904301
2022 METTL14-mediated N6-methyladenosine modification of Pten mRNA inhibits tumour progression in clear-cell renal cell carcinoma. British journal of cancer 40 35249103
2022 Mettl14-Mediated m6A Modification Is Essential for Germinal Center B Cell Response. Journal of immunology (Baltimore, Md. : 1950) 40 35365563
2024 METTL14 downregulation drives S100A4+ monocyte-derived macrophages via MyD88/NF-κB pathway to promote MAFLD progression. Signal transduction and targeted therapy 39 38627387
2023 METTL3 protects METTL14 from STUB1-mediated degradation to maintain m6 A homeostasis. EMBO reports 39 36597993
2023 LncRNA UCA1 promotes keratinocyte-driven inflammation via suppressing METTL14 and activating the HIF-1α/NF-κB axis in psoriasis. Cell death & disease 38 37076497
2019 A Mass Spectrometric Assay of METTL3/METTL14 Methyltransferase Activity. SLAS discovery : advancing life sciences R & D 38 31585521
2024 METTL14-mediated m6A epitranscriptomic modification contributes to chemotherapy-induced neuropathic pain by stabilizing GluN2A expression via IGF2BP2. The Journal of clinical investigation 36 38319733
2022 METTL14-mediated N6-methyladenosine modification of ITGB4 mRNA inhibits metastasis of clear cell renal cell carcinoma. Cell communication and signaling : CCS 36 35305660
2022 LncRNA UCA1 promotes SOX12 expression in breast cancer by regulating m6A modification of miR-375 by METTL14 through DNA methylation. Cancer gene therapy 35 35022519
2023 Adipose METTL14-Elicited N6 -Methyladenosine Promotes Obesity, Insulin Resistance, and NAFLD Through Suppressing β Adrenergic Signaling and Lipolysis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 33 37526326
2019 Acute Deletion of METTL14 in β-Cells of Adult Mice Results in Glucose Intolerance. Endocrinology 33 31369074
2024 METTL14 contributes to acute lung injury by stabilizing NLRP3 expression in an IGF2BP2-dependent manner. Cell death & disease 32 38218935
2023 Targeting histone deacetylase suppresses tumor growth through eliciting METTL14-modified m6 A RNA methylation in ocular melanoma. Cancer communications (London, England) 32 37466203
2024 Small-molecule inhibition of the METTL3/METTL14 complex suppresses neuroblastoma tumor growth and promotes differentiation. Cell reports 31 38691450
2022 DARS-AS1 recruits METTL3/METTL14 to bind and enhance DARS mRNA m6A modification and translation for cytoprotective autophagy in cervical cancer. RNA biology 31 35638109
2023 METTL14 regulates chromatin bivalent domains in mouse embryonic stem cells. Cell reports 30 37314930
2021 TCF4 and HuR mediated-METTL14 suppresses dissemination of colorectal cancer via N6-methyladenosine-dependent silencing of ARRDC4. Cell death & disease 30 34916487
2022 DDX5/METTL3-METTL14/YTHDF2 Axis Regulates Replication of Influenza A Virus. Microbiology spectrum 29 35583334
2024 Impaired binding affinity of YTHDC1 with METTL3/METTL14 results in R-loop accumulation in myelodysplastic neoplasms with DDX41 mutation. Leukemia 28 38514771
2023 METTL14 is decreased and regulates m6 A modification of α-synuclein in Parkinson's disease. Journal of neurochemistry 28 37309980
2023 Smoking and tetramer tryptase accelerate intervertebral disc degeneration by inducing METTL14-mediated DIXDC1 m6 modification. Molecular therapy : the journal of the American Society of Gene Therapy 28 37340635
2022 LncRNA UCA1 Promotes the Progression of AML by Upregulating the Expression of CXCR4 and CYP1B1 by Affecting the Stability of METTL14. Journal of oncology 28 35178087
2020 METTL14 Overexpression Promotes Osteosarcoma Cell Apoptosis and Slows Tumor Progression via Caspase 3 Activation. Cancer management and research 27 33335426
2024 XBP1s activates METTL3/METTL14 for ER-phagy and paclitaxel sensitivity regulation in breast cancer. Cancer letters 24 38582397
2023 METTL14-m6A-FOXO3a axis regulates autophagy and inflammation in ankylosing spondylitis. Clinical immunology (Orlando, Fla.) 24 37935312
2022 Mechanism of METTL14 and m6A modification of lncRNA MALAT1 in the proliferation of oral squamous cell carcinoma cells. Oral diseases 24 35467063
2022 Upregulation of METTL14 contributes to trophoblast dysfunction by elevating FOXO3a expression in an m6A-dependent manner. Placenta 24 35597169
2023 A cancer-associated METTL14 mutation induces aberrant m6A modification, affecting tumor growth. Cell reports 22 37355987
2022 METTL14-dependent m6A modification controls iNKT cell development and function. Cell reports 22 35926466
2023 PRMT1 methylates METTL14 to modulate its oncogenic function. Neoplasia (New York, N.Y.) 20 37269817
2023 METTL14 inhibits malignant progression of oral squamous cell carcinoma by targeting the autophagy-related gene RB1CC1 in an m6A-IGF2BP2-dependent manner. Clinical science (London, England : 1979) 20 37615536
2020 The Distinct Function and Localization of METTL3/METTL14 and METTL16 Enzymes in Cardiomyocytes. International journal of molecular sciences 20 33143367
2024 METTL14 promotes lipid metabolism reprogramming and sustains nasopharyngeal carcinoma progression via enhancing m6A modification of ANKRD22 mRNA. Clinical and translational medicine 19 39021049
2022 Mechanism of METTL14-mediated m6A modification in non-small cell lung cancer cell resistance to cisplatin. Journal of molecular medicine (Berlin, Germany) 19 36352154
2019 The study of METTL3 and METTL14 expressions in childhood ETV6/RUNX1-positive acute lymphoblastic leukemia. Molecular genetics & genomic medicine 19 31429529
2024 Glycolysis Induced by METTL14 Is Essential for Macrophage Phagocytosis and Phenotype in Cervical Cancer. Journal of immunology (Baltimore, Md. : 1950) 18 38197667
2022 RNA binding to human METTL3-METTL14 restricts N6-deoxyadenosine methylation of DNA in vitro. eLife 18 35060905
2021 METTL14-Mediated miR-30c-1-3p Maturation Represses the Progression of Lung Cancer via Regulation of MARCKSL1 Expression. Molecular biotechnology 18 34586620
2019 Knockdown of METTL14 inhibits the growth and invasion of cervical cancer. Translational cancer research 17 35116983
2024 Mycobacterium tuberculosis inhibits METTL14-mediated m6A methylation of Nox2 mRNA and suppresses anti-TB immunity. Cell discovery 16 38548762
2023 The m6A methylation enzyme METTL14 regulates myocardial ischemia/reperfusion injury through the Akt/mTOR signaling pathway. Molecular and cellular biochemistry 16 37436654
2022 Mettl14-mediated m6A modification is essential for visual function and retinal photoreceptor survival. BMC biology 16 35698136
2022 METTL14 promotes migration and invasion of choroidal melanoma by targeting RUNX2 mRNA via m6A modification. Journal of cellular and molecular medicine 16 36264762
2025 JMJD6 K375 acetylation restrains lung cancer progression by enhancing METTL14/m6A/SLC3A2 axis mediated cell ferroptosis. Journal of translational medicine 15 40011892
2022 Mettl14-driven senescence-associated secretory phenotype facilitates somatic cell reprogramming. Stem cell reports 15 35947961
2022 Mettl14-mediated m6A modification enhances the function of Foxp3+ regulatory T cells and promotes allograft acceptance. Frontiers in immunology 15 36341394
2024 METTL14 plays an oncogenic role in NSCLC by modulating ferroptosis and the m6A modification of GPX4. Archives of physiology and biochemistry 14 38993012
2024 METTL14 suppresses the expression of YAP1 and the stemness of triple-negative breast cancer. Journal of experimental & clinical cancer research : CR 14 39563370
2022 Roles of the m6A methyltransferases METTL3, METTL14, and WTAP in pulmonary tuberculosis. Frontiers in immunology 14 36569923
2020 Downregulated METTL14 Expression Correlates with Breast Cancer Tumor Grade and Molecular Classification. BioMed research international 14 33134390