Evidence map›Paper›PMID 37443198›Full record

ArticleNature structural & molecular biology2023

Pre-mRNA splicing order is predetermined and maintains splicing fidelity across multi-intronic transcripts.

Karine Choquet, Autum R Baxter-Koenigs, Sarah-Luisa Dülk, Brendan M Smalec, Silvi Rouskin, L Stirling Churchman

Open access · greenAbstract read
In one paragraph

Article in Nature structural & molecular biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
4.2field-weighted citation impact, top 5% 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

23 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Coupling of alternative splicing and alternative polyadenylation.Acta biochimica et biophysica Sinica · 2024
    Review
  12. Review
  13. Article
  14. Review
  15. RNA exon editing: Splicing the way to treat human diseases.Molecular therapy. Nucleic acids · 2024
    Review
  16. Article
  17. Co-transcriptional gene regulation in eukaryotes and prokaryotes.Nature reviews. Molecular cell biology · 2024
    Review
  18. Review
  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

6 authors at 1 institution in 1 country.

Karine ChoquetDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Autum R Baxter-KoenigsDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Sarah-Luisa DülkDepartment of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Brendan M SmalecDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Silvi RouskinDepartment of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
L Stirling ChurchmanDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA. churchman@genetics.med.harvard.edu.ORCID http://orcid.org/0000-0003-3888-2574
Harvard University · US

Funding

Genetic Analysis and Manipulation Core (GAEC)P50HD105351 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI SCOTT Loren POMEROY, MUSTAFA SAHIN · 2021 to 2026
$9.4M
Global control of co-transcriptional splicingR01GM136794 · NIGMS · HARVARD MEDICAL SCHOOL · PI Lee Stirling Churchman · 2021 to 2026
$3.2M
Direct nanopore detection of modified RNA to probe structure and dynamicsR01HG010538 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI TIMP, WINSTON GEORGE · 2019 to 2022
$3.1M
Direct sequencing of nascent RNA to uncover the functional impact of genetic variants on RNA processingR21HG011682 · NHGRI · HARVARD MEDICAL SCHOOL · PI CHURCHMAN, LEE STIRLING · 2021 to 2021
$455k
Global measurement of splicing kineticsR21HG009264 · NHGRI · HARVARD MEDICAL SCHOOL · PI CHURCHMAN, LEE STIRLING · 2016 to 2017
$431k
NHGRI NIH HHS R01 HG010538NHGRI NIH HHS R21 HG009264NHGRI NIH HHS R21 HG011682NICHD NIH HHS P50 HD105351NIGMS NIH HHS R01 GM136794
6 · The paper itself

Abstract

Combinatorially, intron excision within a given nascent transcript could proceed down any of thousands of paths, each of which would expose different dynamic landscapes of cis-elements and contribute to alternative splicing. In this study, we found that post-transcriptional multi-intron splicing order in human cells is largely predetermined, with most genes spliced in one or a few predominant orders. Strikingly, these orders were conserved across cell types and stages of motor neuron differentiation. Introns flanking alternatively spliced exons were frequently excised last, after their neighboring introns. Perturbations to the spliceosomal U2 snRNA altered the preferred splicing order of many genes, and these alterations were associated with the retention of other introns in the same transcript. In one gene, early removal of specific introns was sufficient to induce delayed excision of three proximal introns, and this delay was caused by two distinct cis-regulatory mechanisms. Together, our results demonstrate that multi-intron splicing order in human cells is predetermined, is influenced by a component of the spliceosome and ensures splicing fidelity across long pre-mRNAs.

Indexed as

RNA PrecursorsRNA SplicingAlternative SplicingHumansIntronsSpliceosomesRNA Precursors

Identifiers

PMID37443198
PMCPMC10653200
OpenAlexW4384198200

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.