Evidence map›Paper›PMID 27244240›Full record

ArticleeLife2016

Single molecule analysis reveals reversible and irreversible steps during spliceosome activation.

Aaron A Hoskins, Margaret L Rodgers, Larry J Friedman, Jeff Gelles, Melissa J Moore

Abstract read
In one paragraph

Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing 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

31 citing papers in PubMed.

  1. Predicting human mRNA isoform levels from site-specific splicing kineticsbioRxiv : the preprint server for biology · 2026
    Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Identification of transient intermediates during spliceosome activation by single molecule fluorescence microscopy.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  9. Review
  10. Multicolor single-molecule FRET for DNA and RNA processes.Current opinion in structural biology · 2021
    Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Structural and functional modularity of the U2 snRNP in pre-mRNA splicing.Critical reviews in biochemistry and molecular biology · 2019
    Review
  17. Review
  18. Article
  19. Article
  20. 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

5 authors.

Aaron A HoskinsDepartment of Biochemistry, University of Wisconsin-Madison, Madison, United States.ORCID 0000-0002-9777-519X
Margaret L RodgersDepartment of Biochemistry, University of Wisconsin-Madison, Madison, United States.
Larry J FriedmanDepartment of Biochemistry, Brandeis University, Waltham, United States.ORCID 0000-0003-4946-8731
Jeff GellesDepartment of Biochemistry, Brandeis University, Waltham, United States.ORCID 0000-0001-7910-3421
Melissa J MooreDepartment of Biochemistry and Molecular Pharmacology, Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, United States.

Funding

Single-molecule visualization of transcription regulation mechanismsR01GM081648 · NIGMS · BRANDEIS UNIVERSITY · PI JEFF GELLES · 2007 to 2026
$7.4M
The second step of pre-mRNA splicingR01GM053007 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI MOORE, MELISSA J. · 1995 to 2018
$5.6M
PREDOCTORAL TRAINING IN MOLECULAR BIOPHYSICST32GM008293 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI JACKSON, MEYER B. · 1989 to 2016
$4.6M
Mechanisms of Spliceosome Assembly and Splice Site RecognitionR01GM112735 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI HOSKINS, AARON ANDREW · 2015 to 2019
$1.6M
Mechanisms of Spliceosome Assembly and Splice Site SelectionR00GM086471 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI HOSKINS, AARON ANDREW · 2011 to 2013
$733k
Howard Hughes Medical InstituteNIGMS NIH HHS R00 GM086471NIGMS NIH HHS R01 GM053007NIGMS NIH HHS R01 GM081648NIGMS NIH HHS R01 GM112735NIGMS NIH HHS T32 GM008293
6 · The paper itself

Abstract

The spliceosome is a complex machine composed of small nuclear ribonucleoproteins (snRNPs) and accessory proteins that excises introns from pre-mRNAs. After assembly the spliceosome is activated for catalysis by rearrangement of subunits to form an active site. How this rearrangement is coordinated is not well-understood. During activation, U4 must be released to allow U6 conformational change, while Prp19 complex (NTC) recruitment is essential for stabilizing the active site. We used multi-wavelength colocalization single molecule spectroscopy to directly observe the key events in Saccharomyces cerevisiae spliceosome activation. Following binding of the U4/U6.U5 tri-snRNP, the spliceosome either reverses assembly by discarding tri-snRNP or proceeds to activation by irreversible U4 loss. The major pathway for NTC recruitment occurs after U4 release. ATP stimulates both the competing U4 release and tri-snRNP discard processes. The data reveal the activation mechanism and show that overall splicing efficiency may be maintained through repeated rounds of disassembly and tri-snRNP reassociation.

Indexed as

RNA SplicingAdenosine TriphosphateCatalytic DomainMolecular Dynamics SimulationRibonucleoprotein, U4-U6 Small NuclearRNA PrecursorsRNA Splicing FactorsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSingle Molecule ImagingSpliceosomesAdenosine TriphosphatePRP19 protein, S cerevisiaeRibonucleoprotein, U4-U6 Small NuclearRNA PrecursorsRNA Splicing FactorsSaccharomyces cerevisiae ProteinsbiochemistrybiophysicsfluorescenceRNAS. cerevisiaesingle-moleculesnRNPspliceosomesplicingstructural biology

Identifiers

PMID27244240
PMCPMC4922858

What OpenQuestion holds

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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.