ArticlePloS one2013
Structure of the arginine methyltransferase PRMT5-MEP50 reveals a mechanism for substrate specificity.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 93 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
93 citing papers in PubMed, 1 synthesis or guideline pooled it, 131 citations in OpenAlex.
- Dietary sulforaphane in cancer chemoprevention: epigenetic regulation and PRMT5-MEP50 complex inhibition-a systematic review.Frontiers in pharmacology · 2026Pooled it
- MTAP Deficiency as a Metabolic Vulnerability in Cancer: Implications for Synthetic Lethal Therapy.Cancer science · 2026Review
- Arginine Methylation in Alternative Splicing: Implications for Cancer Therapy.Journal of cellular physiology · 2026Review
- Affinity purification contaminants identified by cryo-EM and mass spectrometry.Bioscience reports · 2026Article
- Protein arginine methyltransferases in cancer: mechanisms, functions, and therapeutic opportunities.Journal of biomedical science · 2026Review
- LC-MS profiling ofbioRxiv : the preprint server for biology · 2026Article
- Protein arginine methyltransferases in cardiovascular disease: mechanisms, therapeutic potential, and future directions.Frontiers in physiology · 2026Review
- Targeting PRMT5 with indole-based arylsulfonylhydrazides: a novel epigenetic strategy for the treatment of acute and chronic leukemia.American journal of cancer research · 2026Article
- Arginine methylation in cancer: mechanisms and therapeutic implications.Biomarker research · 2025Review
- Productive mRNA chromatin escape is promoted by PRMT5 activity.Molecular cell · 2025Article
- C6orf223 promotes colorectal cancer growth and metastasis by facilitating PRMT5-MEP50 multiprotein complex assembling.The Journal of clinical investigation · 2025Article
- The Role of Protein Arginine Methylation as a Post-Translational Modification in Cellular Homeostasis and Disease.Biology · 2025Review
- CRISPR-Drug Combinatorial Screening Identifies Effective Combination Treatments for MTAP-Deleted Cancer.Cancer research · 2025Article
- PRMT5:MEP50 Are Mediators of Treatment-Induced Neuroendocrine Differentiation in Prostate Cancer.The Prostate · 2025Article
- The PRMT5-splicing axis is a critical oncogenic vulnerability that regulates detained intron splicing.iScience · 2025Article
- In silico protein structural analysis of PRMT5 and RUVBL1 mutations arising in human cancers.Cancer genetics · 2025Article
- PRMT5 inhibition has a potent anti-tumor activity against adenoid cystic carcinoma of salivary glands.Journal of experimental & clinical cancer research : CR · 2025Article
- PRMT5 Inhibitor EPZ015666 Decreases the Viability and Encystment ofMolecules (Basel, Switzerland) · 2024Article
- A review of the known MTA-cooperative PRMT5 inhibitors.RSC advances · 2024Review
- R-Methylation in Plants: A Key Regulator of Plant Development and Response to the Environment.International journal of molecular sciences · 2024Review
33 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
The arginine methyltransferase PRMT5-MEP50 is required for embryogenesis and is misregulated in many cancers. PRMT5 targets a wide variety of substrates, including histone proteins involved in specifying an epigenetic code. However, the mechanism by which PRMT5 utilizes MEP50 to discriminate substrates and to specifically methylate target arginines is unclear. To test a model in which MEP50 is critical for substrate recognition and orientation, we determined the crystal structure of Xenopus laevis PRMT5-MEP50 complexed with S-adenosylhomocysteine (SAH). PRMT5-MEP50 forms an unusual tetramer of heterodimers with substantial surface negative charge. MEP50 is required for PRMT5-catalyzed histone H2A and H4 methyltransferase activity and binds substrates independently. The PRMT5 catalytic site is oriented towards the cross-dimer paired MEP50. Histone peptide arrays and solution assays demonstrate that PRMT5-MEP50 activity is inhibited by substrate phosphorylation and enhanced by substrate acetylation. Electron microscopy and reconstruction showed substrate centered on MEP50. These data support a mechanism in which MEP50 binds substrate and stimulates PRMT5 activity modulated by substrate post-translational modifications.
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Registered trials
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.