Evidence map›Paper›PMID 31485080›Full record

ArticleNature2019

A unified mechanism for intron and exon definition and back-splicing.

Xueni Li, Shiheng Liu, Lingdi Zhang, Aaron Issaian, Ryan C Hill, Sara Espinosa, Shasha Shi, Yanxiang Cui, Kalli Kappel, Rhiju Das and 3 more

Open access · greenAbstract read
In one paragraph

Article in Nature, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
114citing papers in PubMed, 1 pooled it
7.7field-weighted citation impact, top 2% 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

114 citing papers in PubMed, 1 synthesis or guideline pooled it, 181 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Depleting prion protein using splice-switching small molecules.bioRxiv : the preprint server for biology · 2026
    Article
  4. Circular RNA circSmad4 controls pulmonary fibrosis.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2026
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Condensation of ZFP207 and U1 snRNP promotes spliceosome assembly.Nature structural & molecular biology · 2025
    Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article

54 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 1 country.

Xueni LiDepartment of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Shiheng LiuDepartment of Microbiology, Immunology, and Molecular Genetics, UCLA, Los Angeles, CA, USA.
Lingdi ZhangDepartment of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Aaron IssaianDepartment of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Ryan C HillDepartment of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Sara EspinosaDepartment of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Shasha ShiDepartment of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Yanxiang CuiElectron Imaging Center for Nanomachines, UCLA, Los Angeles, CA, USA.
Kalli KappelBiophysics Program, Stanford University, Stanford, CA, USA.
Rhiju DasBiophysics Program, Stanford University, Stanford, CA, USA.
Kirk C HansenDepartment of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Z Hong ZhouDepartment of Microbiology, Immunology, and Molecular Genetics, UCLA, Los Angeles, CA, USA. hong.zhou@ucla.edu.
Rui ZhaoDepartment of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. rui.zhao@cuanschutz.edu.
University of Colorado Anschutz Medical Campus · USImaging Center · USStanford University · USUniversity of California, Los Angeles · US

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
Resource for Biocomputing Visualization and InformaticsP41GM103311 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERRIN, THOMAS E · 2012 to 2017
$8.2M
Next-generation computational/chemical methods for complex RNA structuresR35GM122579 · NIGMS · STANFORD UNIVERSITY · PI Rhiju Das · 2017 to 2026
$7.2M
Genome Structure, Transcription and Packaging of dsRNA VirusesR01AI094386 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Z Hong ZHOU · 2012 to 2026
$6.0M
ChimeraX -- Next Generation Visualization and Analysis Software for Multiscale ModelingR01GM129325 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERRIN, THOMAS E · 2018 to 2025
$5.2M
High-Resolution CryoEM Reconstruction of Large ComplexesR01GM071940 · NIGMS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI ZHOU, Z HONG · 2006 to 2025
$5.0M
Role of Eya3 in regulating the immune microenvironment to promote breast tumor progressionR01CA221282 · NCI · UNIVERSITY OF COLORADO DENVER · PI FORD, HEIDE L., ZHAO, RUI · 2017 to 2021
$3.2M
West/Midwest Consortium for High-Resolution Cryo Electron MicroscopyU24GM116792 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI AGBANDJE-MCKENNA, MAVIS, DOKLAND, TERJE · 2016 to 2020
$3.0M
Understanding the structure and function of U1 snRNPR01GM126157 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI ZHAO, RUI · 2018 to 2021
$1.8M
High-resolution modeling of protein-RNA interfacesR01GM121487 · NIGMS · FRED HUTCHINSON CANCER RESEARCH CENTER · PI BRADLEY, PHILIP · 2017 to 2020
$1.7M
Understanding the structure and function of splicing factor Prp8R01GM080334 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI ZHAO, RUI · 2008 to 2012
$1.5M
Structure and function of U5 snRNPR01GM114178 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI ZHAO, RUI · 2015 to 2018
$1.4M
Howard Hughes Medical InstituteNCI NIH HHS P30 CA046934NCI NIH HHS R21 CA219847NIAID NIH HHS R01 AI094386NIGMS NIH HHS P41 GM103311NIGMS NIH HHS R01 GM071940NIGMS NIH HHS R01 GM121487NIGMS NIH HHS R01 GM126157NIGMS NIH HHS R01 GM129325NIGMS NIH HHS R01 GM130673NIGMS NIH HHS R35 GM122579NIGMS NIH HHS U24 GM116792NIH HHS 1S100D018111NIH HHS 1U24GM116792NIH HHS AI094386NIH HHS CA219847NIH HHS GM121487NIH HHS GM122579NIH HHS GM126157NIH HHS GM130673NIH HHS S10 OD018111
6 · The paper itself

Abstract

The molecular mechanisms of exon definition and back-splicing are fundamental unanswered questions in pre-mRNA splicing. Here we report cryo-electron microscopy structures of the yeast spliceosomal E complex assembled on introns, providing a view of the earliest event in the splicing cycle that commits pre-mRNAs to splicing. The E complex architecture suggests that the same spliceosome can assemble across an exon, and that it either remodels to span an intron for canonical linear splicing (typically on short exons) or catalyses back-splicing to generate circular RNA (on long exons). The model is supported by our experiments, which show that an E complex assembled on the middle exon of yeast EFM5 or HMRA1 can be chased into circular RNA when the exon is sufficiently long. This simple model unifies intron definition, exon definition, and back-splicing through the same spliceosome in all eukaryotes and should inspire experiments in many other systems to understand the mechanism and regulation of these processes.

Indexed as

ExonsIntronsModels, MolecularRNA SplicingCryoelectron MicroscopyProtein Structure, QuaternarySaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSpliceosomesSaccharomyces cerevisiae Proteins

Identifiers

PMID31485080
PMCPMC6939996
OpenAlexW2971559235

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.