Evidence map›Paper›PMID 30639260›Full record

ArticleCell chemical biology2019

Chemical Inhibition of Pre-mRNA Splicing in Living Saccharomyces cerevisiae.

Sarah R Hansen, Brandon J Nikolai, Peyton J Spreacker, Tucker J Carrocci, Aaron A Hoskins

Open access · bronzeAbstract read
In one paragraph

Article in Cell chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

12 citing papers in PubMed, 22 citations in OpenAlex.

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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

5 authors at 1 institution in 1 country.

Sarah R HansenDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Integrated Program in Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
Brandon J NikolaiDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
Peyton J SpreackerDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Integrated Program in Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
Tucker J CarrocciDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Integrated Program in Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
Aaron A HoskinsDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Integrated Program in Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address: ahoskins@wisc.edu.
University of Wisconsin–Madison · US

Funding

BIOTECHNOLOGY TRAINING PROGRAMT32GM008349 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI FOX, BRIAN G · 1989 to 2019
$22.5M
Chemistry-Biology Interface Training ProgramT32GM008505 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI BLACKWELL, HELEN E. · 1993 to 2023
$9.8M
Mechanisms of Spliceosome Assembly and Splice Site RecognitionR01GM112735 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI HOSKINS, AARON ANDREW · 2015 to 2019
$1.6M
NIGMS NIH HHS R01 GM112735NIGMS NIH HHS T32 GM008349NIGMS NIH HHS T32 GM008505
6 · The paper itself

Abstract

The spliceosome mediates precursor mRNA splicing in eukaryotes, including the model organism Saccharomyces cerevisiae (yeast). Despite decades of study, no chemical inhibitors of yeast splicing in vivo are available. We have developed a system to efficiently inhibit splicing and block proliferation in living yeast cells using compounds that target the human spliceosome protein SF3B1. Potent inhibition is observed in yeast expressing a chimeric protein containing portions of human SF3B1. However, only a single point mutation in the yeast homolog of SF3B1 is needed for selective inhibition of splicing by pladienolide B, herboxidiene, or meayamycin in liquid culture. Mutations that enable inhibition also improve splicing of branch sites containing mismatches between the intron and small nuclear RNA-suggesting a link between inhibitor sensitivity and usage of weak branch sites in humans. This approach provides powerful new tools for manipulating splicing in live yeast and studies of spliceosome inhibitors.

Indexed as

Amino Acid SequenceEpoxy CompoundsFatty AlcoholsHumansMacrolidesMutagenesisPhosphoproteinsPyransRibonucleoprotein, U2 Small NuclearRNA PrecursorsRNA SplicingRNA Splicing FactorsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSequence AlignmentSmall Molecule LibrariesEpoxy CompoundsFatty AlcoholsherboxidieneHSH155 protein, S cerevisiaeMacrolidesmeayamycinPhosphoproteinspladienolide BPyransRibonucleoprotein, U2 Small NuclearRNA PrecursorsRNA Splicing FactorsSaccharomyces cerevisiae ProteinsSF3B1 protein, humanSmall Molecule Librariesherboxidieneinhibitormeayamycinpladienolide Bpre-mRNARNASF3B1spliceosomesplicingyeast

Identifiers

PMID30639260
PMCPMC6430687
OpenAlexW2911160787

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.