Evidence map›Paper›PMID 25403181›Full record

ArticleGenes & development2014

Stem-loop 4 of U1 snRNA is essential for splicing and interacts with the U2 snRNP-specific SF3A1 protein during spliceosome assembly.

Shalini Sharma, Somsakul Pop Wongpalee, Ajay Vashisht, James A Wohlschlegel, Douglas L Black

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 2014. 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
–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

46 citing papers in PubMed, 67 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. 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
  6. Journal of Cancer · 2025
    Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
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  15. Article
  16. Article
  17. Review
  18. Article
  19. Early Splicing Complexes and Human Disease.International journal of molecular sciences · 2023
    Review
  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

5 authors at 2 institutions in 1 country.

Shalini SharmaDepartment of Basic Medical Sciences, University of Arizona, College of Medicine-Phoenix, Phoenix, Arizona 85004, USA; Department of Microbiology, Immunology, and Molecular Genetics.
Somsakul Pop WongpaleeMolecular Biology Interdepartmental Graduate Program.
Ajay VashishtDepartment of Biological Chemistry.
James A WohlschlegelDepartment of Biological Chemistry.
Douglas L BlackDepartment of Microbiology, Immunology, and Molecular Genetics, Howard Hughes Medical Institute, University of California at Los Angeles, Los Angeles, California 90095, USA.
University of Arizona · USUniversity of California, Los Angeles · US

Funding

The Regulation of Neuronal Exon SplicingR01GM049662 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BLACK, DOUGLAS L · 1998 to 2019
$6.5M
Proteolytic Control of Iron Metabolism by the Ubiquitin Ligase FBXL5R01GM089778 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WOHLSCHLEGEL, JAMES AKIRA · 2010 to 2023
$4.0M
Examining role of splicing factor mutations in myelodysplastic syndrome (PQ11)R21CA170786 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SHARMA, SHALINI · 2012 to 2013
$366k
Howard Hughes Medical InstituteNCI NIH HHS R21 CA170786NIGMS NIH HHS R01 GM049662NIGMS NIH HHS R01 GM089778NIGMS NIH HHS R01 GM49662
6 · The paper itself

Abstract

The pairing of 5' and 3' splice sites across an intron is a critical step in spliceosome formation and its regulation. Interactions that bring the two splice sites together during spliceosome assembly must occur with a high degree of specificity and fidelity to allow expression of functional mRNAs and make particular alternative splicing choices. Here, we report a new interaction between stem-loop 4 (SL4) of the U1 snRNA, which recognizes the 5' splice site, and a component of the U2 small nuclear ribonucleoprotein particle (snRNP) complex, which assembles across the intron at the 3' splice site. Using a U1 snRNP complementation assay, we found that SL4 is essential for splicing in vivo. The addition of free U1-SL4 to a splicing reaction in vitro inhibits splicing and blocks complex assembly prior to formation of the prespliceosomal A complex, indicating a requirement for a SL4 contact in spliceosome assembly. To characterize the interactions of this RNA structure, we used a combination of stable isotope labeling by amino acids in cell culture (SILAC), biotin/Neutravidin affinity pull-down, and mass spectrometry. We show that U1-SL4 interacts with the SF3A1 protein of the U2 snRNP. We found that this interaction between the U1 snRNA and SF3A1 occurs within prespliceosomal complexes assembled on the pre-mRNA. Thus, SL4 of the U1 snRNA is important for splicing, and its interaction with SF3A1 mediates contact between the 5' and 3' splice site complexes within the assembling spliceosome.

Indexed as

HeLa CellsHumansInverted Repeat SequencesMutationProtein BindingRibonucleoprotein, U2 Small NuclearRNA, Small NuclearRNA Splice SitesRNA SplicingRNA Splicing FactorsSpliceosomesRibonucleoprotein, U2 Small NuclearRNA, Small NuclearRNA Splice SitesRNA Splicing FactorsSF3A1 protein, humanU1 small nuclear RNAalternative splicinggene expressionpre-mRNA splicingribonucleoproteinRNA–protein interactionsnRNAspliceosome

Identifiers

PMID25403181
PMCPMC4233244
OpenAlexW2135924983

What OpenQuestion holds

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LicenceCC BY-NC
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.