Affinage

TRMT11

tRNA (guanine(10)-N(2))-methyltransferase TRMT11 · UniProt Q7Z4G4

Length
463 aa
Mass
53.4 kDa
Annotated
2026-06-10
28 papers in source corpus 11 papers cited in narrative 12 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TRMT11 (yeast Trm11) is the catalytic subunit of a tRNA methyltransferase that installs N2-methylguanosine at position 10 (m2G10) using S-adenosylmethionine as methyl donor, a reaction strictly dependent on the obligate partner subunit TRMT112 (PMID:15899842). TRMT112 activates TRMT11 through a conserved protein–protein interface shared across the Trm112-dependent methyltransferase family, enhancing catalysis by promoting SAM binding and contributing to tRNA substrate engagement; this same surface is used competitively by all of TRMT112's methyltransferase partners (PMID:27986851, PMID:33035335). In human cells TRMT11 is a direct TRMT112 interactor and an active m2G methyltransferase acting on tRNA position 10, and TRMT112 stabilizes TRMT11 protein in cells (PMID:34948388, PMID:37283053). Substrate recognition requires mature tRNA bearing a CCA terminus, a G10-C25 base pair, a regular variable region, and appropriate anticodon-loop contacts, with specific anticodon-loop features acting as negative determinants (PMID:35409407). Functionally, combined loss of TRMT11 and THUMPD3 impairs optimal protein synthesis and cell proliferation, linking the modification to translational fidelity (PMID:37283053).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2005 High

    Established the enzymatic identity of TRMT11 by showing the yeast ortholog is the catalytic subunit of the m2G10 tRNA methyltransferase, requiring Trm112 as an obligate partner.

    Evidence Genetic deletion, in vivo co-IP, and in vitro methyltransferase assay with purified complex in yeast

    PMID:15899842

    Open questions at the time
    • Structural basis of the Trm11-Trm112 interaction not defined
    • Substrate determinants on tRNA not mapped
  2. 2005 Medium

    Linked m2G10 to broader tRNA modification networks via genetic interaction between TRM11 and the m2,2G26 methyltransferase TRM1.

    Evidence Genetic epistasis / double-deletion analysis in yeast

    PMID:15899842

    Open questions at the time
    • No molecular mechanism for the interaction beyond phenotype
    • Functional consequence of combined modification loss unresolved
  3. 2009 Medium

    Confirmed that co-expression of both subunits is sufficient to reconstitute active enzyme, supporting the two-subunit model.

    Evidence Wheat germ cell-free reconstitution followed by methyltransferase activity assay

    PMID:19749381

    Open questions at the time
    • Limited methodological detail
    • Quantitative kinetics not reported
  4. 2011 High

    Defined Trm112 as a common structural activator across multiple methyltransferases, providing a structural model for Trm11-Trm112 activation.

    Evidence X-ray crystallography of Mtq2-Trm112, site-directed mutagenesis, in vivo functional assays, and structural modeling

    PMID:21478168

    Open questions at the time
    • Trm11-Trm112 interface inferred by modeling rather than direct structure
    • Catalytic mechanism not addressed
  5. 2015 High

    Demonstrated that Trm112 uses one conserved surface to activate diverse partners despite low sequence identity, framing Trm11 as one of several competing clients.

    Evidence X-ray crystallography of Trm9-Trm112 and comparative structural analysis of Trm112-MTase complexes

    PMID:26438534

    Open questions at the time
    • Direct Trm11-Trm112 structure still not solved at this point
    • Competition dynamics in vivo unquantified
  6. 2017 High

    Dissected the activation mechanism, showing Trm112 enhances Trm11 activity via effects on SAM binding and tRNA engagement through a shared interface used by all partners.

    Evidence In vitro methyltransferase assays plus hydrogen-deuterium exchange mass spectrometry

    PMID:27986851

    Open questions at the time
    • Atomic-resolution Trm11-Trm112 structure not yet available
    • Kinetic contribution of each effect not separated
  7. 2019 Medium

    Extended the function to archaea and tied the modification to physiology, showing Trm11 produces m2G10/m2,2G10 and supports tRNA stability at high temperature.

    Evidence Gene deletion in T. kodakarensis, LC-MS modification analysis, and high-temperature growth assays

    PMID:31405913

    Open questions at the time
    • Mechanism of thermal stabilization not established
    • Relevance to mesophilic eukaryotic tRNA unclear
  8. 2020 High

    Provided direct structural basis for Trm112-dependent activation through crystal structures of the archaeal Trm11-Trm112 complex and inhibitor-bound Trm11.

    Evidence X-ray crystallography of multiple forms plus comparative in vitro activity assays of Trm11 alone versus complex

    PMID:33035335

    Open questions at the time
    • Human Trm11-Trm112 structure not solved
    • Conformational changes during catalysis not captured
  9. 2022 High

    Mapped the tRNA substrate determinants required for methylation, defining positive and negative recognition elements.

    Evidence In vitro methyltransferase assays with 60 tRNA transcript variants plus tRNA purified from wild-type and trm11 deletion yeast

    PMID:35409407

    Open questions at the time
    • Structural basis of negative determinant exclusion not resolved
    • How determinants generalize across all cellular tRNAs untested
  10. 2023 High

    Confirmed the human enzyme's activity and assigned a cellular function, showing TRMT11 methylates tRNA position 10 and that its loss with THUMPD3 impairs translation and proliferation.

    Evidence Co-IP of TRMT112 interactome in human cells, LC-MS/MS tRNA modification analysis, and siRNA knockdown with translation and proliferation assays

    PMID:37283053

    Open questions at the time
    • Single-knockdown phenotype of TRMT11 alone modest
    • Direct mechanistic link between m2G10 and translational fidelity not defined
  11. 2023 Medium

    Identified an unexpected mRNA substrate, showing yeast Trm11 can m2G-modify mRNA codons and that this impedes ribosomal amino acid addition.

    Evidence LC-MS/MS mRNA modification profiling and reconstituted in vitro translation with modified mRNA

    PMID:37181630

    Open questions at the time
    • mRNA methylation is a novel finding from a single study
    • In vivo prevalence and regulatory role of mRNA m2G unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How m2G10 deposition is regulated in cells and how its loss propagates to translational and proliferative phenotypes in humans remains unresolved.
  • No human TRMT11-TRMT112 structure
  • Physiological role of mRNA methylation undefined
  • Disease association not established in the corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 3 GO:0140098 catalytic activity, acting on RNA 3 GO:0003723 RNA binding 2
Pathway
R-HSA-8953854 Metabolism of RNA 2
Partners
THUMPD3TRMT112
Complex memberships
Trm11-Trm112 tRNA methyltransferase complex

Evidence

Reading pass · 12 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 Yeast Trm11p (ortholog of human TRMT11) is the catalytic subunit of the tRNA m2G10 methyltransferase, which requires Trm112p as an obligate partner subunit; together they catalyze formation of N2-methylguanosine at position 10 in tRNA, using S-adenosylmethionine as methyl donor. Genetic deletion, in vivo co-immunoprecipitation, in vitro methyltransferase assay with purified complex Molecular and cellular biology High 15899842
2005 TRM11 genetically interacts with TRM1 (the m2,2G26 methyltransferase), suggesting that absence of m2G10 and m2,2G26 together affects tRNA metabolism or function. Genetic epistasis / double-deletion analysis in yeast Molecular and cellular biology Medium 15899842
2009 Active yeast Trm11-Trm112 complex was reconstituted in a wheat germ cell-free translation system, confirming that co-expression of both subunits is sufficient to reconstitute m2G10 methyltransferase activity. Cell-free reconstitution (wheat germ cell-free translation) followed by methyltransferase activity assay Nucleic acids symposium series Medium 19749381
2011 Trm112 activates Trm11 (as well as Trm9 and Mtq2) through a common structural mechanism: the Mtq2-Trm112 crystal structure, validated by site-directed mutagenesis and in vivo functional experiments, serves as a model for all three Trm112-methyltransferase complexes including Trm11-Trm112. X-ray crystallography of Mtq2-Trm112 complex, site-directed mutagenesis, in vivo functional assays, structural modeling of Trm11-Trm112 Nucleic acids research High 21478168
2015 Crystal structures of multiple Trm112-methyltransferase complexes reveal structural plasticity: Trm112 uses a similar interaction surface to activate Trm9, Trm11, Bud23, and Mtq2 despite those partners sharing less than 20% sequence identity. X-ray crystallography of Trm9-Trm112 complex; comparative structural analysis of known Trm112-MTase crystal structures Nucleic acids research High 26438534
2017 Trm112 activates Trm11 enzymatic activity by influencing S-adenosyl-L-methionine (SAM) binding and by contributing to tRNA substrate binding; hydrogen-deuterium exchange mass spectrometry showed the Trm11-Trm112 interaction relies on the same molecular interface as other Trm112-methyltransferase complexes, meaning all Trm112-dependent methyltransferases compete for the same binding surface on Trm112. Enzymatic activity assays (in vitro methyltransferase), hydrogen-deuterium exchange coupled to mass spectrometry (HDX-MS) Nucleic acids research High 27986851
2019 Archaeal Trm11 (ortholog) from Thermococcus kodakarensis is required for formation of m2G10 and m2,2G10 in tRNA; deletion of trm11 results in poor growth at 95°C, indicating the m2,2G10 modification contributes to tRNA stabilization at high temperatures. Gene deletion in T. kodakarensis, LC-MS tRNA modification analysis, growth phenotype assay at high temperature Journal of bacteriology Medium 31405913
2020 Crystal structures of the Archaeoglobus fulgidus Trm11-Trm112 complex and of Trm11 alone (or bound to sinefungin inhibitor) reveal the molecular basis of Trm112-dependent activation: AfTrm11 is active as a single protein but its enzymatic activity is strongly enhanced by AfTrm112, and the interaction resembles eukaryotic Trm11-Trm112 complexes. X-ray crystallography, in vitro methyltransferase activity assays comparing Trm11 alone vs. Trm11-Trm112 complex Nucleic acids research High 33035335
2021 Human TRMT112 (the activator hub) interacts with TRMT11 along with six other methyltransferases; TRMT112 stabilizes all partner MTases including TRMT11 in cells, and single amino acid mutations on the TRMT112 surface reveal differential binding contributions across partners. SILAC co-immunoprecipitation screen (pulldown of TRMT112), western blot stability assays, site-directed mutagenesis of TRMT112 International journal of molecular sciences Medium 34948388
2022 The eukaryotic Trm11-Trm112 complex requires specific tRNA structural elements for methylation: mature tRNA (not precursor) with CCA terminus, a regular-size variable region, G10-C25 base pair, and anticodon-loop contacts are needed; U38 in tRNAAla and U32-A38 base pair in tRNACys act as negative determinants. In vitro methyltransferase assays with 60 tRNA transcript variants; purification of tRNAValAAC1 from wild-type and trm11 deletion yeast strains International journal of molecular sciences High 35409407
2023 Human TRMT11, identified as a direct partner of TRMT112 in intact human cells, is an active N2-methylguanosine (m2G) methyltransferase that methylates position 10 of tRNAs; combined loss of TRMT11 and THUMPD3 impairs optimal protein synthesis and cell proliferation. Co-immunoprecipitation of TRMT112 interactome in human cells, LC-MS/MS tRNA modification analysis, siRNA knockdown with translation and proliferation assays Nucleic acids research High 37283053
2023 Yeast Trm11 incorporates N2-methylguanosine (m2G) into mRNA codons in addition to tRNA; m2G introduced into mRNA codons impedes amino acid addition by the ribosome in a position-dependent manner, as shown in a reconstituted translation system. LC-MS/MS mRNA modification profiling, mRNA purification, reconstituted in vitro translation assay with modified mRNA substrates RSC chemical biology Medium 37181630

Source papers

Stage 0 corpus · 28 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Trm11p and Trm112p are both required for the formation of 2-methylguanosine at position 10 in yeast tRNA. Molecular and cellular biology 101 15899842
2014 Two-subunit enzymes involved in eukaryotic post-transcriptional tRNA modification. RNA biology 92 25625329
2011 Mechanism of activation of methyltransferases involved in translation by the Trm112 'hub' protein. Nucleic acids research 67 21478168
2019 Identification of recurrent fusion genes across multiple cancer types. Scientific reports 51 30705370
2008 tRNA and protein methylase complexes mediate zymocin toxicity in yeast. Molecular microbiology 50 18657261
2017 Trm112, a Protein Activator of Methyltransferases Modifying Actors of the Eukaryotic Translational Apparatus. Biomolecules 49 28134793
2011 Formation of m2G6 in Methanocaldococcus jannaschii tRNA catalyzed by the novel methyltransferase Trm14. Nucleic acids research 38 21693558
2018 Evolutionary insights into Trm112-methyltransferase holoenzymes involved in translation between archaea and eukaryotes. Nucleic acids research 36 30010922
2015 Insights into molecular plasticity in protein complexes from Trm9-Trm112 tRNA modifying enzyme crystal structure. Nucleic acids research 35 26438534
2017 Activation mode of the eukaryotic m2G10 tRNA methyltransferase Trm11 by its partner protein Trm112. Nucleic acids research 33 27986851
2023 N 2-methylguanosine modifications on human tRNAs and snRNA U6 are important for cell proliferation, protein translation and pre-mRNA splicing. Nucleic acids research 29 37283053
2019 Detection of fusion transcripts in the serum samples of patients with hepatocellular carcinoma. Oncotarget 27 31164957
2021 Human TRMT112-Methyltransferase Network Consists of Seven Partners Interacting with a Common Co-Factor. International journal of molecular sciences 26 34948388
2019 Distinct Modified Nucleosides in tRNATrp from the Hyperthermophilic Archaeon Thermococcus kodakarensis and Requirement of tRNA m2G10/m22G10 Methyltransferase (Archaeal Trm11) for Survival at High Temperatures. Journal of bacteriology 26 31405913
2023 Methylated guanosine and uridine modifications in S. cerevisiae mRNAs modulate translation elongation. RSC chemical biology 24 37181630
2012 Germline predictors of androgen deprivation therapy response in advanced prostate cancer. Mayo Clinic proceedings 19 22386179
2021 Detection of fusion gene transcripts in the blood samples of prostate cancer patients. Scientific reports 14 34417538
2020 Structural and functional insights into Archaeoglobus fulgidus m2G10 tRNA methyltransferase Trm11 and its Trm112 activator. Nucleic acids research 13 33035335
2009 Production of yeast (m2G10) methyltransferase (Trm11 and Trm112 complex) in a wheat germ cell-free translation system. Nucleic acids symposium series (2004) 13 19749381
2022 Duodenal inflammation in common variable immunodeficiency has altered transcriptional response to viruses. The Journal of allergy and clinical immunology 12 36220400
2022 Calorie restriction remodels gut microbiota and suppresses tumorigenesis of colorectal cancer in mice. Experimental and therapeutic medicine 12 36588818
2022 Sex-determining Region Y-box transcription factor 13 promotes breast cancer cell proliferation and glycolysis by activating the tripartite motif containing 11-mediated Wnt/β-catenin signaling pathway. Bioengineered 9 35611828
2022 Required Elements in tRNA for Methylation by the Eukaryotic tRNA (Guanine-N2-) Methyltransferase (Trm11-Trm112 Complex). International journal of molecular sciences 7 35409407
2023 Targeted Profiling of Epitranscriptomic Reader, Writer, and Eraser Proteins Regulated by H3K36me3. Analytical chemistry 4 37296074
2020 Germline variants and response to systemic therapy in advanced prostate cancer. Pharmacogenomics 3 31849283
2025 The Landscape of tRNA Modifications in Archaea. bioRxiv : the preprint server for biology 2 40654657
2024 AtTRM11 as a tRNA 2-methylguanosine methyltransferase modulates flowering and bacterial resistance via translational regulation. Plant science : an international journal of experimental plant biology 2 39716634
2025 Identification and validation of biomarkers related to nicotinamide metabolic pathway activity in heart failure. Frontiers in genetics 0 41477636

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