ArticleNucleic acids research2024
The diversity of splicing modifiers acting on A-1 bulged 5'-splice sites reveals rules for rational drug design.
Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 18 citations in OpenAlex.
- ChemBioParis 2025: Approaching Biology Through Chemistry in the City of Light.Chembiochem : a European journal of chemical biology · 2026Article
- Specificity and exon target space of splicing modifying compounds.Nature communications · 2026Article
- Conformational analysis of nucleic acids for optimizing DNA and RNA topological models.Nucleic acids research · 2026Article
- Structural Pockets and Interacting RNA-Associated Ligands (SPIRAL): A DSSR-enabled Meta-Analysis of RNA-Small Molecule Recognition.bioRxiv : the preprint server for biology · 2026Article
- Tunable gene control via RNA splicing with a clinically approved small molecule.Nature communications · 2026Article
- An approach for the systematic profiling of drug-induced remodeling of RNA-RBP (RNA-binding protein) interactions.RSC advances · 2026Article
- RNA functional modulation by Mitoxantrone via RNA structural ensemble repartitioning.Nature communications · 2026Article
- A Chemically Induced CRISPR/dCas13Journal of medicinal chemistry · 2025Article
- Small Molecule Approach to RNA Targeting Binder Discovery (SMARTBind) Using Deep Learning Without Structural Input.bioRxiv : the preprint server for biology · 2025Article
- MVRBind: multi-view learning for RNA-small molecule binding site prediction.Briefings in bioinformatics · 2025Article
- Steering research on mRNA splicing in cancer towards clinical translation.Nature reviews. Cancer · 2024Review
- DeepRSMA: a cross-fusion-based deep learning method for RNA-small molecule binding affinity prediction.Bioinformatics (Oxford, England) · 2024Article
- Therapeutic targeting of RNA for neurological and neuromuscular disease.Genes & development · 2024Review
- Splice-modifying drug mechanisms.Nature chemical biology · 2024Article
- Engineered Branaplam Aptamers Exploit Structural Elements from Natural Riboswitches.ACS chemical biology · 2024Article
- Small molecules modulating RNA splicing: a review of targets and future perspectives.RSC medicinal chemistry · 2024Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Pharmacological modulation of RNA splicing by small molecules is an emerging facet of drug discovery. In this context, the SMN2 splicing modifier SMN-C5 was used as a prototype to understand the mode of action of small molecule splicing modifiers and propose the concept of 5'-splice site bulge repair. In this study, we combined in vitro binding assays and structure determination by NMR spectroscopy to identify the binding modes of four other small molecule splicing modifiers that switch the splicing of either the SMN2 or the HTT gene. Here, we determined the solution structures of risdiplam, branaplam, SMN-CX and SMN-CY bound to the intermolecular RNA helix epitope containing an unpaired adenine within the G-2A-1G+1U+2 motif of the 5'-splice site. Despite notable differences in their scaffolds, risdiplam, SMN-CX, SMN-CY and branaplam contact the RNA epitope similarly to SMN-C5, suggesting that the 5'-splice site bulge repair mechanism can be generalised. These findings not only deepen our understanding of the chemical diversity of splicing modifiers that target A-1 bulged 5'-splice sites, but also identify common pharmacophores required for modulating 5'-splice site selection with small molecules.
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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.