Evidence mapPaperPMID 40339124Full record

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.

Tianshuo Liu, Ling Xu, Kevin Chung, Luke J Sisto, Jimin Hwang, Chengxin Zhang, Michael C Van Zandt, Anna Marie Pyle

Abstract read
In one paragraph

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.

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. Article
  3. Article
  4. Article
  5. ACS chemical biology · 2026
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Tianshuo Liu *Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511.
Ling Xu *Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511.
Kevin Chung *Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511.
Luke J SistoDepartment of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511.
Jimin HwangDepartment of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511.
Chengxin ZhangDepartment of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511.
Michael C Van ZandtNew England Discovery Partners, Branford, CT 06405.
Anna Marie PyleDepartment of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511.

Funding

Yale Pathology Tissue Services Shared ResourceP30CA016359 · NCI · YALE UNIVERSITY · 1985 to 2025
$13.5M
HHS | National Institutes of Health (NIH) S10OD023603NCI NIH HHS P30 CA016359NIH HHS S10 OD023603
6 · The paper itself

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.

Indexed as

IntronsRNARNA, FungalSmall Molecule LibrariesCryoelectron MicroscopyLigandsModels, MolecularNucleic Acid ConformationRNA SplicingStructure-Activity RelationshipLigandsRNARNA, FungalSmall Molecule LibrariescryoEMhigh-throughput screeningRNA–ligand recognitionRNA-targeting ligandssplicing inhibitor

Identifiers

PMID40339124
PMCPMC12088405

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.