ArticleNucleic acids research2019
Mechanism of allosteric activation of human mRNA cap methyltransferase (RNMT) by RAM: insights from accelerated molecular dynamics simulations.
Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 35 citations in OpenAlex.
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- Targeting RNA binding proteins with small-molecule inhibitors: Advances, challenges, and therapeutic opportunities.Acta pharmaceutica Sinica. B · 2026Review
- Advances in research on RNA methylation and its role in the immune microenvironment of gastrointestinal tumors.Frontiers in cell and developmental biology · 2026Review
- RNA methylation modifications in neurodegenerative diseases: Focus on their enzyme system.Journal of advanced research · 2025Review
- RNMT-dependent RNA cap methylation in health and disease.The Biochemical journal · 2025Review
- N7-methylguanosine (m7G) modification in breast cancer: clinical significances and molecular mechanisms.Cancer cell international · 2025Review
- RNA triphosphatase-mediated mRNA capping is essential for maintaining transcript homeostasis and the survival of Toxoplasma gondii.Nature communications · 2025Article
- RNA epigenetic modifications as dynamic biomarkers in cancer: from mechanisms to clinical translation.Biomarker research · 2025Review
- Identification and validation of hub m7G-related genes and infiltrating immune cells in osteoarthritis based on integrated computational and bioinformatics analysis.BMC musculoskeletal disorders · 2025Article
- Characterisation of RNA guanine-7 methyltransferase (RNMT) using a small molecule approach.The Biochemical journal · 2025Article
- Deciphering the secret codes in NClinical and translational medicine · 2025Review
- N7-methylguanosine modification in cancers: from mechanisms to therapeutic potential.Journal of hematology & oncology · 2025Review
- The role of m5C, m1A and m7G modifications in tumors of urinary system.Frontiers in cell and developmental biology · 2025Review
- The Role of mRNA Modifications in Bone Diseases.International journal of biological sciences · 2025Review
- RNA methylation and breast cancer: insights into m6A, m7G and m5C.Molecular biology reports · 2024Review
- A review of current developments in RNA modifications in lung cancer.Cancer cell international · 2024Review
- Regulations of mFrontiers of medicine · 2024Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The RNA guanine-N7 methyltransferase (RNMT) in complex with RNMT-activating miniprotein (RAM) catalyses the formation of a N7-methylated guanosine cap structure on the 5' end of nascent RNA polymerase II transcripts. The mRNA cap protects the primary transcript from exonucleases and recruits cap-binding complexes that mediate RNA processing, export and translation. By using microsecond standard and accelerated molecular dynamics simulations, we provide for the first time a detailed molecular mechanism of allosteric regulation of RNMT by RAM. We show that RAM selects the RNMT active site conformations that are optimal for binding of substrates (AdoMet and the cap), thus enhancing their affinity. Furthermore, our results strongly suggest the likely scenario in which the cap binding promotes the subsequent AdoMet binding, consistent with the previously suggested cooperative binding model. By employing the network community analyses, we revealed the underlying long-range allosteric networks and paths that are crucial for allosteric regulation by RAM. Our findings complement and explain previous experimental data on RNMT activity. Moreover, this study provides the most complete description of the cap and AdoMet binding poses and interactions within the enzyme's active site. This information is critical for the drug discovery efforts that consider RNMT as a promising anti-cancer target.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.