ArticleNucleic acids research2016
Molecular basis of RNA guanine-7 methyltransferase (RNMT) activation by RAM.
Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed.
- Discovery of a 4'-Azido Fleximer Nucleoside Analog With Broad-Spectrum Antiviral Activity Against DENV, EBOV, and Other RNA Viruses.ChemMedChem · 2026Article
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- Defining substrate specificities of human RNA capping methyltransferases through quantitative assessment of independent yet cooperative activities.Protein science : a publication of the Protein Society · 2026Article
- RNA methylation in autoimmune rheumatic diseases: mechanisms and therapeutic potential.Frontiers in immunology · 2026Review
- RNA modifications: roles in immune cell biology and tumor regulation.Cancer cell international · 2025Review
- RNA modifications in health and disease: from mechanistic insights to therapeutic applications.Precision clinical medicine · 2025Review
- Review
- RNMT-dependent RNA cap methylation in health and disease.The Biochemical journal · 2025Review
- Structural basis for sensitivity and acquired resistance of fungal cap guanine-N7 methyltransferases to the antifungal antibiotic sinefungin.Nucleic acids research · 2025Article
- Characterisation of RNA guanine-7 methyltransferase (RNMT) using a small molecule approach.The Biochemical journal · 2025Article
- N7-methylguanosine modification in cancers: from mechanisms to therapeutic potential.Journal of hematology & oncology · 2025Review
- Neuroblastoma susceptibility and association of N7-methylguanosine modification gene polymorphisms: multi-center case-control study.Pediatric research · 2025Article
- Article
- Exploring the exoproteome of the parasitic nematodeFrontiers in immunology · 2025Article
- eIF4E orchestrates mRNA processing, RNA export and translation to modify specific protein production.Nucleus (Austin, Tex.) · 2024Review
- SHIFTR enables the unbiased identification of proteins bound to specific RNA regions in live cells.Nucleic acids research · 2024Article
- Drug Discovery in Low Data Regimes: Leveraging a Computational Pipeline for the Discovery of Novel SARS-CoV-2 Nsp14-MTase Inhibitors.bioRxiv : the preprint server for biology · 2024Article
- RAM is upregulated during T cell activation and is required for RNA cap formation and gene expression.Discovery immunology · 2024Article
- M7G-related tumor immunity: novel insights of RNA modification and potential therapeutic targets.International journal of biological sciences · 2024Review
- Exploring the impact of metabolites function on heart failure and coronary heart disease: insights from a Mendelian randomization (MR) study.American journal of cardiovascular disease · 2024Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Maturation and translation of mRNA in eukaryotes requires the addition of the 7-methylguanosine cap. In vertebrates, the cap methyltransferase, RNA guanine-7 methyltransferase (RNMT), has an activating subunit, RNMT-Activating Miniprotein (RAM). Here we report the first crystal structure of the human RNMT in complex with the activation domain of RAM. A relatively unstructured and negatively charged RAM binds to a positively charged surface groove on RNMT, distal to the active site. This results in stabilisation of a RNMT lobe structure which co-evolved with RAM and is required for RAM binding. Structure-guided mutagenesis and molecular dynamics simulations reveal that RAM stabilises the structure and positioning of the RNMT lobe and the adjacent α-helix hinge, resulting in optimal positioning of helix A which contacts substrates in the active site. Using biophysical and biochemical approaches, we observe that RAM increases the recruitment of the methyl donor, AdoMet (S-adenosyl methionine), to RNMT. Thus we report the mechanism by which RAM allosterically activates RNMT, allowing it to function as a molecular rheostat for mRNA cap methylation.
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Registered trials
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