ArticleNature communications2024
A sequential binding mechanism for 5' splice site recognition and modulation for the human U1 snRNP.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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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
9 citing papers in PubMed.
- The U1 snRNP protein U1C and Helix H of U1 snRNA are critical for small molecule splicing modulator function.Nature communications · 2026Article
- Predicting human mRNA isoform levels from site-specific splicing kineticsbioRxiv : the preprint server for biology · 2026Article
- GPATCH11 ortholog Sap34 regulates pre-mRNA splicing by interacting with early spliceosomal complexes in Schizosaccharomyces pombe.Scientific reports · 2026Article
- Uncovering dual molecular diagnoses in families with complex phenotypes through structural and clinical studies of novel COL4A6 variants.QJM : monthly journal of the Association of Physicians · 2026Observational
- Nascent RNA Folding and RNP Assembly Revealed by Single-molecule Microscopy.Journal of molecular biology · 2026Review
- U1 RNA Detected by Toll-Like Receptor 3 Plays a Role in the Pathogenesis of Pterygium.Investigative ophthalmology & visual science · 2025Article
- QKI ensures splicing fidelity during cardiogenesis by engaging the U6 tri-snRNP to activate splicing at weak 5' splice sites.bioRxiv : the preprint server for biology · 2025Article
- Alternative Splicing: A Critical Regulator in Human Bone Biology and Tumor Progression.Research (Washington, D.C.) · 2025Review
- Branch site recognition by the spliceosome.RNA (New York, N.Y.) · 2024Review
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4 authors.
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Abstract
Splice site recognition is essential for defining the transcriptome. Drugs like risdiplam and branaplam change how human U1 snRNP recognizes particular 5' splice sites (5'SS) and promote U1 snRNP binding and splicing at these locations. Despite the therapeutic potential of 5'SS modulators, the complexity of their interactions and snRNP substrates have precluded defining a mechanism for 5'SS modulation. We have determined a sequential binding mechanism for modulation of -1A bulged 5'SS by branaplam using a combination of ensemble kinetic measurements and colocalization single molecule spectroscopy (CoSMoS). Our mechanism establishes that U1-C protein binds reversibly to U1 snRNP, and branaplam binds to the U1 snRNP/U1-C complex only after it has engaged with a -1A bulged 5'SS. Obligate orders of binding and unbinding explain how reversible branaplam interactions cause formation of long-lived U1 snRNP/5'SS complexes. Branaplam targets a ribonucleoprotein, not only an RNA duplex, and its action depends on fundamental properties of 5'SS recognition.
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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.