Evidence map›Paper›PMID 37402368›Full record

ArticleMolecular cell2023

Targeted high-throughput mutagenesis of the human spliceosome reveals its in vivo operating principles.

Irene Beusch, Beiduo Rao, Michael K Studer, Tetiana Luhovska, Viktorija Šukytė, Susan Lei, Juan Oses-Prieto, Em SeGraves, Alma Burlingame, Stefanie Jonas and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
5.1field-weighted citation impact, top 4% 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

28 citing papers in PubMed, 33 citations in OpenAlex.

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  13. Cancer-associated SF3B1 mutation K700E causes widespread changes in U2/branchpoint recognition without altering splicing.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  14. Review
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  16. Building the first base editors.Nature chemical biology · 2025
    Article
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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 at 2 institutions in 2 countries.

Irene BeuschDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, USA.
Beiduo RaoDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, USA.
Michael K StuderInstitute of Molecular Biology and Biophysics, Department of Biology, ETH Zurich, Zurich, Switzerland.
Tetiana LuhovskaInstitute of Molecular Biology and Biophysics, Department of Biology, ETH Zurich, Zurich, Switzerland.
Viktorija ŠukytėInstitute of Molecular Biology and Biophysics, Department of Biology, ETH Zurich, Zurich, Switzerland.
Susan LeiDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, USA.
Juan Oses-PrietoDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, USA.
Em SeGravesDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, USA.
Alma BurlingameDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, USA.
Stefanie JonasInstitute of Molecular Biology and Biophysics, Department of Biology, ETH Zurich, Zurich, Switzerland.
Hiten D MadhaniDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, USA. Electronic address: hitenmadhani@gmail.com.
University of California, San Francisco · USETH Zurich · CH

Funding

Mechanisms of Gene SilencingR01GM071801 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Hiten D Madhani · 2005 to 2026
$7.1M
Illumina NovaSeq 6000 Sequencing SystemS10OD028511 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHOW, ERIC D · 2020 to 2020
$583k
NIGMS NIH HHS R01 GM071801NIH HHS S10 OD028511
6 · The paper itself

Abstract

The spliceosome is a staggeringly complex machine, comprising, in humans, 5 snRNAs and >150 proteins. We scaled haploid CRISPR-Cas9 base editing to target the entire human spliceosome and investigated the mutants using the U2 snRNP/SF3b inhibitor, pladienolide B. Hypersensitive substitutions define functional sites in the U1/U2-containing A complex but also in components that act as late as the second chemical step after SF3b is dissociated. Viable resistance substitutions map not only to the pladienolide B-binding site but also to the G-patch domain of SUGP1, which lacks orthologs in yeast. We used these mutants and biochemical approaches to identify the spliceosomal disassemblase DHX15/hPrp43 as the ATPase ligand for SUGP1. These and other data support a model in which SUGP1 promotes splicing fidelity by triggering early spliceosome disassembly in response to kinetic blocks. Our approach provides a template for the analysis of essential cellular machines in humans.

Indexed as

Epoxy CompoundsSpliceosomesHumansMacrolidesMutagenesisRNA SplicingSaccharomyces cerevisiaeEpoxy CompoundsMacrolidespladienolide B

Identifiers

PMID37402368
PMCPMC10484158
OpenAlexW4382930623

What OpenQuestion holds

Textmetadata
LicenceTDM
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.