Evidence map›Paper›PMID 34301950›Full record

ArticleNature communications2021

Structural basis of intron selection by U2 snRNP in the presence of covalent inhibitors.

Constantin Cretu, Patricia Gee, Xiang Liu, Anant Agrawal, Tuong-Vi Nguyen, Arun K Ghosh, Andrew Cook, Melissa Jurica, Nicholas A Larsen, Vladimir Pena

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
3.7field-weighted citation impact, top 5% of its field
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

46 citing papers in PubMed, 63 citations in OpenAlex.

  1. Review
  2. Article
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  5. Spirocyclic β-lactone secondary metabolites modulate spliceosome function.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  8. RNA Splicing as a Therapeutic Target in Cancer.Annual review of pharmacology and toxicology · 2026
    Review
  9. Article
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  15. Article
  16. Review
  17. Targeting RNA splicing modulation: new perspectives for anticancer strategy?Journal of experimental & clinical cancer research : CR · 2025
    Review
  18. Review
  19. Article
  20. Review
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

10 authors at 3 institutions in 3 countries.

Constantin CretuResearch Group Mechanisms and Regulation of Splicing, The Institute of Cancer Research, London, UK.
Patricia GeeH3 Biomedicine, Inc, Cambridge, MA, USA.
Xiang LiuH3 Biomedicine, Inc, Cambridge, MA, USA.
Anant AgrawalH3 Biomedicine, Inc, Cambridge, MA, USA.
Tuong-Vi NguyenH3 Biomedicine, Inc, Cambridge, MA, USA.
Arun K GhoshDepartments of Chemistry and Medicinal Chemistry, Purdue University, West Lafayette, IN, USA.
Andrew CookH3 Biomedicine, Inc, Cambridge, MA, USA.
Melissa JuricaDepartment of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, CA, USA.ORCID 0000-0002-4488-1386
Nicholas A LarsenH3 Biomedicine, Inc, Cambridge, MA, USA.
Vladimir PenaResearch Group Mechanisms and Regulation of Splicing, The Institute of Cancer Research, London, UK. vlad.pena@icr.ac.uk.
Institute of Cancer Research · GBPurdue University West Lafayette · USUniversity of California, Santa Cruz · US

Funding

Mechanisms of the spliceosome protein SF3B1 and inhibitorsR01GM122279 · NIGMS · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI JURICA, MELISSA S · 2017 to 2020
$1.8M
NIGMS NIH HHS R01 GM122279Wellcome Trust 220300
6 · The paper itself

Abstract

Intron selection during the formation of prespliceosomes is a critical event in pre-mRNA splicing. Chemical modulation of intron selection has emerged as a route for cancer therapy. Splicing modulators alter the splicing patterns in cells by binding to the U2 snRNP (small nuclear ribonucleoprotein)-a complex chaperoning the selection of branch and 3' splice sites. Here we report crystal structures of the SF3B module of the U2 snRNP in complex with spliceostatin and sudemycin FR901464 analogs, and the cryo-electron microscopy structure of a cross-exon prespliceosome-like complex arrested with spliceostatin A. The structures reveal how modulators inactivate the branch site in a sequence-dependent manner and stall an E-to-A prespliceosome intermediate by covalent coupling to a nucleophilic zinc finger belonging to the SF3B subunit PHF5A. These findings support a mechanism of intron recognition by the U2 snRNP as a toehold-mediated strand invasion and advance an unanticipated drug targeting concept.

Indexed as

Cryoelectron MicroscopyCrystallography, X-RayDNAHumansIntronsLactonesModels, MolecularNucleic Acid ConformationProtein BindingProtein ConformationPyransPyronesRibonucleoprotein, U2 Small NuclearSpiro CompoundsSpliceosomesDNAFR 901464LactonesPyransPyronesRibonucleoprotein, U2 Small NuclearSpiro Compoundsspliceostatin Aspliceostatin E

Identifiers

PMID34301950
PMCPMC8302644
OpenAlexW3184326956

What OpenQuestion holds

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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 OpenQuestion graph.