ArticleProceedings of the National Academy of Sciences of the United States of America2025
Molecular insights into de novo small-molecule recognition by an intron RNA structure.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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.
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Who cites it
5 citing papers in PubMed.
- RNA functional modulation by Mitoxantrone via RNA structural ensemble repartitioning.Nature communications · 2026Article
- Pre-splicing conformation and stepwise circularization of a group I intron in Azoarcus pre-tRNA.Nature communications · 2026Article
- Three-dimensional structure of the palbociclib-HIV TAR complex.Nucleic acids research · 2026Article
- The kinase inhibitor palbociclib binds to HIV TAR RNA with very low nanomolar affinity and exquisite specificity.Nucleic acids research · 2026Article
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Authors and funding
8 authors.
Funding
Abstract
Despite the promise of vastly expanding the druggable genome, rational design of RNA-targeting ligands remains challenging as it requires the rapid identification of hits and visualization of the resulting cocomplexes for guiding optimization. Here, we leveraged high-throughput screening, medicinal chemistry, and structural biology to identify a de novo splicing inhibitor against a large and highly folded fungal group I intron. High-resolution cryoEM structures of the intron in different liganded states not only reveal molecular interactions that rationalize experimental structure-activity relationship but also shed light on a unique strategy whereby RNA-associated metal ions and RNA conformation exhibit exceptional plasticity in response to small-molecule binding. This study reveals general principles that govern RNA-ligand recognition, the interplay between chemical bonding specificity, and dynamic responses within an RNA target.
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Registered trials
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