ArticleNature communications2022
A small molecule antagonist of SMN disrupts the interaction between SMN and RNAP II.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Sodium Channel Blockers Demonstrate Binding Affinity for the Tandem Tudor Domain of the Epigenetic Hub UHRF1.ChemMedChem · 2026Article
- KIF5A downregulation in spinal muscular atrophy links axonal regeneration defects with ALS.JCI insight · 2026Article
- Molecular rotor-based probes for protein monitoring in biomedical research.Nature reviews. Chemistry · 2026Review
- RNA-binding proteins TDP-43 and FUS promote R-loop resolution and regulate transcription termination.The Journal of biological chemistry · 2026Article
- Review
- Predicting fragment binding modes using customized Lennard-Jones potentials in short molecular dynamics simulations.Computational and structural biotechnology journal · 2025Article
- Article
- In Search of Spinal Muscular Atrophy Disease Modifiers.International journal of molecular sciences · 2024Review
- Exploring Aromatic Cage Flexibility Using Cosolvent Molecular Dynamics Simulations─An In-Silico Case Study of Tudor Domains.Journal of chemical information and modeling · 2024Article
- Loss of the methylarginine reader function of SND1 confers resistance to hepatocellular carcinoma.The Biochemical journal · 2023Article
- Pharmacological perturbation of the phase-separating protein SMNDC1.Nature communications · 2023Article
- Tudor-dimethylarginine interactions: the condensed version.Trends in biochemical sciences · 2023Review
- [Molecular pathological mechanism of liver metabolic disorder in mice with severe spinal muscular atrophy].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
- Effectors and effects of arginine methylation.Biochemical Society transactions · 2023Article
- Protein arginine methylation in transcription and epigenetic regulation.Frontiers in epigenetics and epigenomics · 2023Review
Corrections and comments
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Authors and funding
21 authors at 3 institutions in 3 countries.
Funding
Abstract
Survival of motor neuron (SMN) functions in diverse biological pathways via recognition of symmetric dimethylarginine (Rme2s) on proteins by its Tudor domain, and deficiency of SMN leads to spinal muscular atrophy. Here we report a potent and selective antagonist with a 4-iminopyridine scaffold targeting the Tudor domain of SMN. Our structural and mutagenesis studies indicate that both the aromatic ring and imino groups of compound 1 contribute to its selective binding to SMN. Various on-target engagement assays support that compound 1 specifically recognizes SMN in a cellular context and prevents the interaction of SMN with the R1810me2s of RNA polymerase II subunit POLR2A, resulting in transcription termination and R-loop accumulation mimicking SMN depletion. Thus, in addition to the antisense, RNAi and CRISPR/Cas9 techniques, potent SMN antagonists could be used as an efficient tool to understand the biological functions of SMN.
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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.