ArticleJournal of the American Chemical Society2015
Inhibition of Non-ATG Translational Events in Cells via Covalent Small Molecules Targeting RNA.
Article in Journal of the American Chemical Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- RNA Drugs and RNA Targets for Small Molecules: Principles, Progress, and Challenges.Pharmacological reviews · 2020Pooled it
- Predicting small molecule-RNA interactions without RNA tertiary structures.Nature biotechnology · 2026Article
- SHAPE-Based Chemical Probes for Studying preQACS chemical biology · 2025Article
- RNA-Focused DNA-Encoded Library Construction, Screening, and Integration of Docking Identify Bioactive Ligands of Pathogenic r(GbioRxiv : the preprint server for biology · 2025Article
- Structure-Guided Design of a Bioactive Covalent Small Molecule Targeting a Riboswitch.Journal of the American Chemical Society · 2025Article
- Covalent Probes Reveal Small-Molecule Binding Pockets in Structured RNA and Enable Bioactive Compound Design.Journal of the American Chemical Society · 2025Article
- Discovery of RNA-Reactive Small Molecules Guides the Design of Electrophilic Modules for RNA-Specific Covalent Binders.Journal of the American Chemical Society · 2025Article
- Streamlined Fragment-Based Discovery Platform for Targeting Structured RNAs.ACS chemical biology · 2025Article
- Engineering covalent small molecule-RNA complexes in living cells.Nature chemical biology · 2025Article
- The Druggable Transcriptome Project: From Chemical Probes to Precision Medicines.Biochemistry · 2025Review
- Mapping small molecule-RNA binding sites via Chem-CLIP synergized with capillary electrophoresis and nanopore sequencing.Nucleic acids research · 2025Article
- Synthesis of HBC fluorophores with an electrophilic handle for covalent attachment to Pepper RNA.Beilstein journal of organic chemistry · 2025Article
- Targeting RNA with small molecules, from RNA structures to precision medicines: IUPHAR review: 40.British journal of pharmacology · 2024Review
- Transcriptome-Wide, Unbiased Profiling of Ribonuclease Targeting Chimeras.Journal of the American Chemical Society · 2024Article
- Transcriptome-Wide Studies of RNA-Targeted Small Molecules Provide a Simple and Selective r(CUG)ACS central science · 2023Article
- Chemical RNA Cross-Linking: Mechanisms, Computational Analysis, and Biological Applications.JACS Au · 2023Review
- Study of an RNA-Focused DNA-Encoded Library Informs Design of a Degrader of a r(CUG) Repeat Expansion.Journal of the American Chemical Society · 2022Article
- Small Molecule Screening Discovers Compounds that Reduce FMRpolyG Protein Aggregates and Splicing Defect Toxicity in Fragile X-Associated Tremor/Ataxia Syndrome.Molecular neurobiology · 2022Article
- C9orf72 ALS/FTD dipeptide repeat protein levels are reduced by small molecules that inhibit PKA or enhance protein degradation.The EMBO journal · 2022Article
- Ribonuclease recruitment using a small molecule reduced c9ALS/FTD r(GScience translational medicine · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
One major class of disease-causing RNAs is expanded repeating transcripts. These RNAs cause diseases via multiple mechanisms, including: (i) gain-of-function, in which repeating RNAs bind and sequester proteins involved in RNA biogenesis and (ii) repeat associated non-ATG (RAN) translation, in which repeating transcripts are translated into toxic proteins without use of a canonical, AUG, start codon. Herein, we develop and study chemical probes that bind and react with an expanded r(CGG) repeat (r(CGG)(exp)) present in a 5' untranslated region that causes fragile X-associated tremor/ataxia syndrome (FXTAS). Reactive compounds bind to r(CGG)(exp) in cellulo as shown with Chem-CLIP-Map, an approach to map small molecule binding sites within RNAs in cells. Compounds also potently improve FXTAS-associated pre-mRNA splicing and RAN translational defects, while not affecting translation of the downstream open reading frame. In contrast, oligonucleotides affect both RAN and canonical translation when they bind to r(CGG)(exp), which is mechanistically traced to a decrease in polysome loading. Thus, designer small molecules that react with RNA targets can be used to profile the RNAs to which they bind in cells, including identification of binding sites, and can modulate several aspects of RNA-mediated disease pathology in a manner that may be more beneficial than oligonucleotides.
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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.