Evidence map›Paper›PMID 40437193›Full record

ArticleNature chemistry2025

Structure-informed design of an ultrabright RNA-activated fluorophore.

Mo Yang, Peri R Prestwood, Luiz F M Passalacqua, Sumirtha Balaratnam, Christopher R Fullenkamp, J Winston Arney, Kevin M Weeks, Adrian Ferre-D'Amare, John S Schneekloth

Abstract read
In one paragraph

Article in Nature chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Fluorogenic Covalent Probes for RNA.Journal of the American Chemical Society · 2025
    Article
  5. Sequence and ionic requirements of pUG fold quadruplexes.bioRxiv : the preprint server for biology · 2025
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Mo Yang *Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.ORCID 0000-0002-8487-3866
Peri R Prestwood *Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.ORCID 0009-0008-6453-4307
Luiz F M PassalacquaLaboratory of Nucleic Acids, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-5490-2427
Sumirtha BalaratnamChemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.
Christopher R FullenkampChemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.ORCID 0000-0002-9479-896X
J Winston ArneyDepartment of Chemistry, University of North Carolina, Chapel Hill, NC, USA.
Kevin M WeeksDepartment of Chemistry, University of North Carolina, Chapel Hill, NC, USA.ORCID 0000-0002-6748-9985
Adrian Ferre-D'AmareLaboratory of Nucleic Acids, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0003-4549-1619
John S SchneeklothChemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA. schneeklothjs@mail.nih.gov.ORCID 0000-0001-7459-783X

Funding

Identification of Nucleic Acid Binding Small MoleculesZIABC011585 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI SCHNEEKLOTH, JOHN · 2014 to 2025
$18.6M
RNA: Tools for Cell BiologyZIAHL006188 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI FERRÉ-D'AMARÉ, ADRIAN · 2014 to 2025
$9.5M
Discovery and Function of Higher-Order RNA StructureR35GM122532 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Kevin M Weeks · 2017 to 2026
$5.7M
Intramural NIH HHS ZIA BC011585Intramural NIH HHS ZIA HL006188NIGMS NIH HHS R35 GM122532U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) 1ZIABC011585-08U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) 1ZIAHL006188-08U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) ZIAHL006188
6 · The paper itself

Abstract

RNA-based fluorogenic aptamers, such as Mango, are uniquely powerful tools for imaging RNA that activate the fluorescence of a weakly or non-fluorescent small molecule when bound. A central challenge has been to develop brighter, more specific and high-affinity aptamer-ligand systems for cellular imaging. Here we report an ultrabright fluorophore for the Mango II system discovered using a structure-informed, fragment-based small-molecule microarray approach. This dye-termed SALAD1 (structure-informed, array-enabled LigAnD 1)-exhibits subnanomolar aptamer affinity and 3.5-fold brighter fluorescence than Mango II-TO1-biotin pair, a widely used fluorogenic system. Performance was improved by modulating RNA-dye molecular recognition without altering the fluorophore's π-system. High-resolution X-ray structures reveal the binding mode for SALAD1, which exhibits improved pocket occupancy, a more defined binding pose and a unique bonding interaction with potassium. SALAD1 is cell-permeable and facilitates improved in-cell confocal RNA imaging. This work introduces an additional RNA-activated fluorophore demonstrating how fragment-based ligand discovery can be used to create high-performance ligands for RNA targets.

Indexed as

Aptamers, NucleotideFluorescent DyesRNACrystallography, X-RayHumansLigandsModels, MolecularAptamers, NucleotideFluorescent DyesLigandsRNA

Identifiers

PMID40437193
PMCPMC12329784

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Registered trials

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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.