Affinage

TRMT11

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

Length
463 aa
Mass
53.4 kDa
Annotated
2026-04-28
28 papers in source corpus 12 papers cited in narrative 13 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TRMT11 is the catalytic subunit of a conserved SAM-dependent methyltransferase that installs N2-methylguanosine (m2G) at position 10 of tRNAs and also modifies mRNA substrates. TRMT11 forms an obligate heterodimeric complex with the allosteric activator TRMT112, which enhances enzymatic activity by promoting SAM cofactor binding and contributing directly to tRNA substrate recognition through a conserved interaction interface shared across multiple Trm112-dependent methyltransferases (PMID:15899842, PMID:27986851, PMID:33035335). The complex requires mature tRNAs bearing a CCA terminus, a regular-size variable loop, and a G10–C25 base pair for efficient methylation, and combined loss of TRMT11 with the related m2G methyltransferase THUMPD3 impairs protein synthesis and cell proliferation (PMID:35409407, PMID:37283053). TRMT11 additionally methylates mRNA guanosines to m2G, and this modification impedes translation elongation in a codon-position-dependent manner (PMID:37181630).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 2005 High

    Identification of Trm11 as the catalytic subunit responsible for m2G10 formation on tRNA, and discovery that it requires the obligate partner Trm112 for activity, established the enzymatic identity and minimal complex composition of this methyltransferase.

    Evidence Co-immunoprecipitation, gene deletion, and in vitro methyltransferase assays in S. cerevisiae

    PMID:15899842

    Open questions at the time
    • No structural information on how Trm112 activates Trm11
    • Substrate specificity determinants on tRNA unknown
    • No human ortholog characterization
  2. 2008 Medium

    Demonstration that Trm11 competes with Trm9, Mtq2, and Lys9 for Trm112 binding revealed that Trm112 is a shared and limiting partner, raising the question of how cells balance multiple Trm112-dependent methyltransferase activities.

    Evidence Co-immunoprecipitation and overexpression competition assays in yeast

    PMID:18657261

    Open questions at the time
    • Quantitative binding affinities not determined
    • Physiological consequences of competition not assessed in vivo
  3. 2011 High

    Crystal structure of the related Mtq2–Trm112 complex combined with mutagenesis showed that Trm112 employs a conserved interaction interface to activate multiple methyltransferases including Trm11, providing the first structural framework for understanding allosteric activation.

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

    PMID:21478168

    Open questions at the time
    • Direct crystal structure of Trm11–Trm112 not yet solved
    • Mechanism by which Trm112 enhances SAM binding to Trm11 not determined
  4. 2017 High

    HDX-MS and biochemical analyses demonstrated that Trm112 activates Trm11 by influencing both SAM binding and tRNA substrate recognition, delineating the dual mechanistic roles of the activating subunit.

    Evidence HDX-MS, in vitro methyltransferase assays, and mutagenesis on yeast Trm11–Trm112

    PMID:27986851

    Open questions at the time
    • No structure of Trm11–Trm112 bound to tRNA substrate
    • Relative contributions of SAM-binding enhancement vs. tRNA recognition to overall activity not quantified
  5. 2020 High

    Crystal structures of archaeal Trm11 alone and in complex with Trm112 revealed that Trm11 possesses basal monomeric activity that is strongly enhanced by Trm112, and confirmed evolutionary conservation of the interaction interface from archaea to eukaryotes.

    Evidence X-ray crystallography of AfTrm11 and AfTrm11–AfTrm112, in vitro activity assays

    PMID:33035335

    Open questions at the time
    • No eukaryotic Trm11 crystal structure available
    • Structural basis for tRNA recognition by the complex still unresolved
  6. 2022 High

    Systematic substrate mapping with 60 tRNA variants defined the recognition requirements of Trm11–Trm112 — mature CCA-bearing tRNA, a regular variable loop, and the G10–C25 base pair — resolving which tRNA features determine substrate selectivity.

    Evidence In vitro methyltransferase assays with tRNA transcript variants and in vivo modification analysis in yeast

    PMID:35409407

    Open questions at the time
    • Structural basis for anticodon-loop recognition not determined
    • How negative determinants (e.g. U38) mechanistically block methylation is unclear
  7. 2023 High

    Validation that human TRMT11 is an active m2G10 tRNA methyltransferase partnered with TRMT112, and that combined loss of TRMT11 and THUMPD3 reduces protein synthesis and proliferation, established the physiological relevance of m2G modification in human cells.

    Evidence Co-IP, LC-MS/MS tRNA modification profiling, knockdown with translation and proliferation readouts in human cells

    PMID:37283053

    Open questions at the time
    • Individual contribution of TRMT11 loss to translational phenotype obscured by redundancy with THUMPD3
    • Full human tRNA substrate repertoire not mapped
  8. 2023 Medium

    Discovery that Trm11 also methylates mRNA to form m2G, and that m2G in mRNA codons impedes translation elongation, expanded the substrate repertoire of this enzyme beyond tRNA.

    Evidence LC-MS/MS mRNA modification quantification in trm11Δ yeast and reconstituted in vitro translation

    PMID:37181630

    Open questions at the time
    • mRNA methylation by TRMT11 not confirmed in human cells
    • Specificity determinants for mRNA substrate selection unknown
    • Physiological significance of mRNA m2G modification in vivo not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • No structure of a eukaryotic Trm11–Trm112 complex bound to tRNA exists, and the physiological consequences of TRMT11 loss in mammalian organisms remain poorly defined.
  • No eukaryotic Trm11 crystal or cryo-EM structure with tRNA substrate
  • No animal model of TRMT11 deficiency
  • Relative in vivo mRNA vs tRNA methylation activity not quantified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 8
Pathway
R-HSA-8953854 Metabolism of RNA 4 R-HSA-392499 Metabolism of proteins 2
Partners
TRMT112
Complex memberships
Trm11–Trm112 methyltransferase complex

Evidence

Reading pass · 13 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, forming an obligate two-subunit complex with Trm112p (a zinc-binding protein) to catalyze N2-methylguanosine formation at position 10 of tRNA, using S-adenosylmethionine as the methyl donor. In vivo co-immunoprecipitation, gene deletion analysis, in vitro methyltransferase activity assay Molecular and cellular biology High 15899842
2005 TRM11 genetically interacts with TRM1 in yeast, suggesting that the absence of m2G10 and m2,2G26 affects tRNA metabolism or functioning; deletion of TRM11 alone has no detectable phenotype under standard laboratory conditions. Genetic epistasis (double gene deletion analysis) Molecular and cellular biology Medium 15899842
2008 Trm11 competes with Trm9, Lys9, and Mtq2 for binding to Trm112, such that overexpression of Trm11 or other Trm112 partners can interfere with formation of the Trm9-Trm112 complex, as shown by co-immunoprecipitation studies. Co-immunoprecipitation, overexpression competition assay Molecular microbiology Medium 18657261
2009 Active yeast Trm11-Trm112 complex can be reconstituted in a wheat germ cell-free translation system, confirming that the two subunits are sufficient for enzymatic activity. Cell-free protein synthesis (wheat germ system), in vitro methyltransferase activity assay Nucleic acids symposium series (2004) Medium 19749381
2011 Trm112 activates the Trm11-Trm112 tRNA methyltransferase complex using a structural mechanism common to other Trm112-methyltransferase complexes, as determined by the 3D crystal structure of the Mtq2-Trm112 complex and site-directed mutagenesis; Trm112 uses a conserved interaction interface to activate multiple different methyltransferases. X-ray crystallography, site-directed mutagenesis, in vivo functional assays Nucleic acids research High 21478168
2015 Structural comparison of Trm112-methyltransferase complexes (including Trm11-Trm112) revealed that Trm112 uses a structurally plastic but common binding mode to interact with multiple methyltransferase partners sharing less than 20% sequence identity. X-ray crystallography (Trm9-Trm112 crystal structure), structural comparison Nucleic acids research High 26438534
2017 Trm112 activates Trm11 enzymatic activity by influencing S-adenosyl-L-methionine (SAM) binding and by contributing directly to tRNA substrate binding; hydrogen-deuterium exchange mass spectrometry confirmed that the Trm11-Trm112 interaction relies on the same molecular interface as other Trm112-methyltransferase complexes. In vitro methyltransferase activity assay, hydrogen-deuterium exchange coupled to mass spectrometry (HDX-MS), mutagenesis Nucleic acids research High 27986851
2019 In hyperthermophilic archaeon Thermococcus kodakarensis, the archaeal Trm11 ortholog is required for m2,2G10 formation on tRNA; the Δtrm11 strain grew poorly at 95°C, indicating that this modification is important for tRNA stability/folding at high temperatures. Gene deletion, LC/MS-based tRNA modification analysis, growth phenotype assay Journal of bacteriology High 31405913
2020 Crystal structures of archaeal AfTrm11 alone and in complex with AfTrm112 (and with the methyltransferase inhibitor sinefungin) showed that AfTrm11 is active as a monomer but its activity is strongly enhanced by AfTrm112, and the Trm11-Trm112 interaction interface is conserved between archaea and eukaryotes. X-ray crystallography, in vitro methyltransferase activity assay, protein interaction assays Nucleic acids research High 33035335
2021 Human TRMT112 pulls down TRMT11 as one of seven methyltransferase partners in human cells (SILAC screen), and TRMT112 stabilizes TRMT11 protein levels; single amino acid mutations on TRMT112 surface differentially affect its interaction with different MTase partners. SILAC-based pulldown/mass spectrometry, western blot, co-immunoprecipitation, site-directed mutagenesis International journal of molecular sciences High 34948388
2022 The Saccharomyces cerevisiae Trm11-Trm112 complex requires: (1) mature tRNA with CCA terminus (not precursor tRNA), (2) a regular-size variable region, (3) the G10-C25 base pair, and (4) recognizes the anticodon loop; U38 in tRNAAla and the U32-A38 base pair in tRNACys negatively affect methylation. In vitro methyltransferase assay with 60 tRNA transcript variants, tRNA purification from wild-type and trm11 deletion yeast strains International journal of molecular sciences High 35409407
2023 Human TRMT11 is a direct partner of human TRMT112 in intact cells and 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. Proximity ligation/co-immunoprecipitation in intact cells, LC-MS/MS modification profiling, knockdown with translation and proliferation readouts Nucleic acids research High 37283053
2023 Trm11 (yeast) also methylates mRNA guanosine residues to form N2-methylguanosine (m2G) in S. cerevisiae mRNAs, and introduction of m2G into mRNA codons impedes amino acid addition during translation elongation in a position-dependent manner. LC-MS/MS quantification of mRNA modifications in trm11 deletion strains, reconstituted in vitro translation system 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 100 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 66 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 37 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 31 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 27 37283053
2019 Detection of fusion transcripts in the serum samples of patients with hepatocellular carcinoma. Oncotarget 27 31164957
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 25 31405913
2021 Human TRMT112-Methyltransferase Network Consists of Seven Partners Interacting with a Common Co-Factor. International journal of molecular sciences 23 34948388
2023 Methylated guanosine and uridine modifications in S. cerevisiae mRNAs modulate translation elongation. RSC chemical biology 21 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
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 Calorie restriction remodels gut microbiota and suppresses tumorigenesis of colorectal cancer in mice. Experimental and therapeutic medicine 12 36588818
2020 Structural and functional insights into Archaeoglobus fulgidus m2G10 tRNA methyltransferase Trm11 and its Trm112 activator. Nucleic acids research 11 33035335
2022 Duodenal inflammation in common variable immunodeficiency has altered transcriptional response to viruses. The Journal of allergy and clinical immunology 10 36220400
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 1 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 1 39716634
2025 Identification and validation of biomarkers related to nicotinamide metabolic pathway activity in heart failure. Frontiers in genetics 0 41477636