Evidence map›Paper›PMID 33660780›Full record

ArticleNucleic acids research2021

Disruption of exon-bridging interactions between the minor and major spliceosomes results in alternative splicing around minor introns.

Anouk M Olthof, Alisa K White, Stephen Mieruszynski, Karen Doggett, Madisen F Lee, Almahdi Chakroun, Alice K Abdel Aleem, Justine Rousseau, Cinzia Magnani, Chaim M Roifman and 3 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

24 citing papers in PubMed, 34 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Human mutation · 2026
    Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Saturation genome editing ofmedRxiv : the preprint server for health sciences · 2025
    Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Role of RNA Splicing Mutations in Diffuse Large B Cell Lymphoma.International journal of general medicine · 2023
    Review
  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

13 authors at 7 institutions in 5 countries.

Anouk M OlthofPhysiology and Neurobiology Department, University of Connecticut, 75 N. Eagleville Road, Storrs, CT 06269, USA.
Alisa K WhitePhysiology and Neurobiology Department, University of Connecticut, 75 N. Eagleville Road, Storrs, CT 06269, USA.
Stephen MieruszynskiEpigenetics and Development Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
Karen DoggettEpigenetics and Development Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
Madisen F LeePhysiology and Neurobiology Department, University of Connecticut, 75 N. Eagleville Road, Storrs, CT 06269, USA.
Almahdi ChakrounNeurogenetics, Weill Cornell Medicine-Qatar, Doha, Qatar.
Alice K Abdel AleemNeurogenetics, Weill Cornell Medicine-Qatar, Doha, Qatar.
Justine RousseauCHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada.
Cinzia MagnaniNeonatology and Neonatal Intensive Care Unit, Maternal and Child Department, University of Parma, Parma, 43121, Italy.
Chaim M RoifmanDivision of Immunology and Allergy, Department of Pediatrics, The Hospital for Sick Children and the University of Toronto, Toronto, ON M5G 1X8, Canada.
Philippe M CampeauDepartment of Pediatrics, University of Montreal, Montreal, QC H4A 3J1, Canada.
Joan K HeathEpigenetics and Development Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
Rahul N KanadiaPhysiology and Neurobiology Department, University of Connecticut, 75 N. Eagleville Road, Storrs, CT 06269, USA.
University of Connecticut · USWalter and Eliza Hall Institute of Medical Research · AUWeill Cornell Medical College in Qatar · QACentre Hospitalier Universitaire Sainte-Justine · CAUniversité de Montréal · CAUniversity of Parma · ITUniversity of Toronto · CA

Funding

Understanding the role of minor intron splicing in cortical developmentR01NS102538 · NINDS · UNIVERSITY OF CONNECTICUT STORRS · PI KANADIA, RAHUL N · 2018 to 2022
$1.8M
Understanding the Role of Minor Spliceosome in Cortical DevelopmentR21NS096684 · NINDS · UNIVERSITY OF CONNECTICUT STORRS · PI KANADIA, RAHUL N · 2016 to 2017
$420k
NINDS NIH HHS R01 NS102538NINDS NIH HHS R21 NS096684
6 · The paper itself

Abstract

Vertebrate genomes contain major (>99.5%) and minor (<0.5%) introns that are spliced by the major and minor spliceosomes, respectively. Major intron splicing follows the exon-definition model, whereby major spliceosome components first assemble across exons. However, since most genes with minor introns predominately consist of major introns, formation of exon-definition complexes in these genes would require interaction between the major and minor spliceosomes. Here, we report that minor spliceosome protein U11-59K binds to the major spliceosome U2AF complex, thereby supporting a model in which the minor spliceosome interacts with the major spliceosome across an exon to regulate the splicing of minor introns. Inhibition of minor spliceosome snRNAs and U11-59K disrupted exon-bridging interactions, leading to exon skipping by the major spliceosome. The resulting aberrant isoforms contained a premature stop codon, yet were not subjected to nonsense-mediated decay, but rather bound to polysomes. Importantly, we detected elevated levels of these alternatively spliced transcripts in individuals with minor spliceosome-related diseases such as Roifman syndrome, Lowry-Wood syndrome and early-onset cerebellar ataxia. In all, we report that the minor spliceosome informs splicing by the major spliceosome through exon-definition interactions and show that minor spliceosome inhibition results in aberrant alternative splicing in disease.

Indexed as

Alternative SplicingExonsIntronsAnimalsApoptosis Regulatory ProteinsCardiomyopathiesCells, CulturedCerebellar AtaxiaGrowth DisordersHumansIntellectual DisabilityMiceMicrocephalyNonsense Mediated mRNA DecayOsteochondrodysplasiasPolyribosomesApoptosis Regulatory ProteinsPDCD7 protein, humanRNA, Small NuclearTranscription Factors

Identifiers

PMID33660780
PMCPMC8034651
OpenAlexW3133950746

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.