Evidence map›Paper›PMID 38898052›Full record

ArticleNature communications2024

Targeting the conserved active site of splicing machines with specific and selective small molecule modulators.

Ilaria Silvestri, Jacopo Manigrasso, Alessandro Andreani, Nicoletta Brindani, Caroline Mas, Jean-Baptiste Reiser, Pietro Vidossich, Gianfranco Martino, Andrew A McCarthy, Marco De Vivo and 1 more

Abstract read
In one paragraph

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 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing 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

13 citing papers in PubMed.

  1. Article
  2. Article
  3. Controlled dynamic remodeling of the spliceosome active site enables the first step of splicing.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. Molecular insights into de novo small-molecule recognition by an intron RNA structure.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. 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

11 authors.

Ilaria SilvestriLaboratory of Molecular Modelling & Drug Discovery, Istituto Italiano di Tecnologia, Via Morego 30, 16163, Genoa, Italy.ORCID http://orcid.org/0000-0003-0640-755X
Jacopo ManigrassoLaboratory of Molecular Modelling & Drug Discovery, Istituto Italiano di Tecnologia, Via Morego 30, 16163, Genoa, Italy.
Alessandro AndreaniLaboratory of Molecular Modelling & Drug Discovery, Istituto Italiano di Tecnologia, Via Morego 30, 16163, Genoa, Italy.
Nicoletta BrindaniLaboratory of Molecular Modelling & Drug Discovery, Istituto Italiano di Tecnologia, Via Morego 30, 16163, Genoa, Italy.ORCID http://orcid.org/0000-0002-7928-4207
Caroline MasUniv. Grenoble Alpes, CNRS, CEA, EMBL, ISBG, F-38000, Grenoble, France.ORCID http://orcid.org/0000-0002-7733-6982
Jean-Baptiste ReiserUniv. Grenoble Alpes, CNRS, CEA, IBS, F-38000, Grenoble, France.ORCID http://orcid.org/0000-0001-6926-9137
Pietro VidossichLaboratory of Molecular Modelling & Drug Discovery, Istituto Italiano di Tecnologia, Via Morego 30, 16163, Genoa, Italy.
Gianfranco MartinoLaboratory of Molecular Modelling & Drug Discovery, Istituto Italiano di Tecnologia, Via Morego 30, 16163, Genoa, Italy.
Andrew A McCarthyEuropean Molecular Biology Laboratory (EMBL) Grenoble, 71 Avenue des Martyrs, Grenoble, 38042, France.ORCID http://orcid.org/0000-0003-4478-0136
Marco De VivoLaboratory of Molecular Modelling & Drug Discovery, Istituto Italiano di Tecnologia, Via Morego 30, 16163, Genoa, Italy. marco.devivo@iit.it.ORCID http://orcid.org/0000-0003-4022-5661
Marco MarciaEuropean Molecular Biology Laboratory (EMBL) Grenoble, 71 Avenue des Martyrs, Grenoble, 38042, France. mmarcia@embl.fr.ORCID http://orcid.org/0000-0003-2430-0713

Funding

Agence Nationale de la Recherche (French National Research Agency) ANR-10-INSB-05-02Agence Nationale de la Recherche (French National Research Agency) ANR-17-EURE-0003Fondation ARC pour la Recherche sur le Cancer (ARC Foundation for Cancer Research) PJA-20191209284
6 · The paper itself

Abstract

The self-splicing group II introns are bacterial and organellar ancestors of the nuclear spliceosome and retro-transposable elements of pharmacological and biotechnological importance. Integrating enzymatic, crystallographic, and simulation studies, we demonstrate how these introns recognize small molecules through their conserved active site. These RNA-binding small molecules selectively inhibit the two steps of splicing by adopting distinctive poses at different stages of catalysis, and by preventing crucial active site conformational changes that are essential for splicing progression. Our data exemplify the enormous power of RNA binders to mechanistically probe vital cellular pathways. Most importantly, by proving that the evolutionarily-conserved RNA core of splicing machines can recognize small molecules specifically, our work provides a solid basis for the rational design of splicing modulators not only against bacterial and organellar introns, but also against the human spliceosome, which is a validated drug target for the treatment of congenital diseases and cancers.

Indexed as

Catalytic DomainIntronsRNA SplicingSpliceosomesHumansSmall Molecule LibrariesSmall Molecule Libraries

Identifiers

PMID38898052
PMCPMC11187226

What OpenQuestion holds

Textmetadata
LicenceCC BY
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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 OpenQuestion graph.