Evidence map›Paper›PMID 25970246›Full record

ArticleNature2015

Recursive splicing in long vertebrate genes.

Christopher R Sibley, Warren Emmett, Lorea Blazquez, Ana Faro, Nejc Haberman, Michael Briese, Daniah Trabzuni, Mina Ryten, Michael E Weale, John Hardy and 5 more

Abstract read
In one paragraph

Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.

0numbers the graph read from it
0cells of the map it votes in
97citing 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

97 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Detection of a sequence feature for recursive splicing.bioRxiv : the preprint server for biology · 2026
    Article
  8. Article
  9. Review
  10. Article
  11. The "cutting edge" of non-canonical RNA splicing.Frontiers in molecular biosciences · 2026
    Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Christopher R Sibley *Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK.
Warren Emmett *University College London Genetics Institute, Gower Street, London WC1E 6BT, UK.
Lorea BlazquezDepartment of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK.
Ana FaroDepartment of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.
Nejc HabermanDepartment of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK.
Michael BrieseMRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
Daniah TrabzuniDepartment of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK.
Mina RytenDepartment of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK.
Michael E WealeKing's College London, Department of Medical & Molecular Genetics, Guy's Hospital, London SE1 9RT, UK.
John HardyDepartment of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK.
Miha ModicMRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
Tomaž CurkFaculty of Computer and Information Science, University of Ljubljana, Ljubljana, Slovenia.
Stephen W WilsonDepartment of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.
Vincent PlagnolUniversity College London Genetics Institute, Gower Street, London WC1E 6BT, UK.
Jernej UleDepartment of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK.

Funding

European Research Council 206726European Research Council 617837Medical Research Council G0802462Medical Research Council G0901254Medical Research Council MC_U105185858Medical Research Council U105185858Wellcome Trust 104682
6 · The paper itself

Abstract

It is generally believed that splicing removes introns as single units from precursor messenger RNA transcripts. However, some long Drosophila melanogaster introns contain a cryptic site, known as a recursive splice site (RS-site), that enables a multi-step process of intron removal termed recursive splicing. The extent to which recursive splicing occurs in other species and its mechanistic basis have not been examined. Here we identify highly conserved RS-sites in genes expressed in the mammalian brain that encode proteins functioning in neuronal development. Moreover, the RS-sites are found in some of the longest introns across vertebrates. We find that vertebrate recursive splicing requires initial definition of an 'RS-exon' that follows the RS-site. The RS-exon is then excluded from the dominant mRNA isoform owing to competition with a reconstituted 5' splice site formed at the RS-site after the first splicing step. Conversely, the RS-exon is included when preceded by cryptic promoters or exons that fail to reconstitute an efficient 5' splice site. Most RS-exons contain a premature stop codon such that their inclusion can decrease mRNA stability. Thus, by establishing a binary splicing switch, RS-sites demarcate different mRNA isoforms emerging from long genes by coupling cryptic elements with inclusion of RS-exons.

Indexed as

AnimalsAnkyrinsBase SequenceBrainCell Adhesion Molecule-1Cell Adhesion MoleculesCodon, TerminatorDrosophila melanogasterExonsFemaleFrontal LobeHumansImmunoglobulinsIntronsMalePromoter Regions, GeneticANK3 protein, humanAnkyrinsCADM1 protein, humanCadm2a protein, zebrafishCADM2 protein, humanCell Adhesion Molecule-1Cell Adhesion MoleculesCodon, TerminatorImmunoglobulinsRNA IsoformsRNA Splice SitesZebrafish Proteins

Identifiers

PMID25970246
PMCPMC4471124

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Registered trials

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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.