Evidence map›Paper›PMID 32402057›Full record

ArticleNucleic acids research2020

Structural disruption of exonic stem-loops immediately upstream of the intron regulates mammalian splicing.

Kaushik Saha, Whitney England, Mike Minh Fernandez, Tapan Biswas, Robert C Spitale, Gourisankar Ghosh

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

22 citing papers in PubMed, 30 citations in OpenAlex.

  1. Review
  2. CAR-SPLASH identifies nascent pre-mRNA structures implicated in kinetic coupling and alternative splicing.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Chemical Probing of RNA Structure In Vivo Using SHAPE-MaP and DMS-MaP.Methods in molecular biology (Clifton, N.J.) · 2023
    Article
  9. SHAPE to Probe RNA Structure and RNA-Protein Interactions In Vitro.Methods in molecular biology (Clifton, N.J.) · 2023
    Article
  10. Article
  11. Donor Splice Site Variant inMedicina (Kaunas, Lithuania) · 2022
    Article
  12. Secondary structures in RNA synthesis, splicing and translation.Computational and structural biotechnology journal · 2022
    Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Transcription Regulation Through Nascent RNA Folding.Journal of molecular biology · 2021
    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 2 institutions in 1 country.

Kaushik SahaDepartment of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0375, USA.
Whitney EnglandDepartment of Pharmaceutical Sciences, University of California Irvine, 147 Bison Modular, Building 515, Irvine, CA 92697, USA.
Mike Minh FernandezDepartment of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0375, USA.
Tapan BiswasDepartment of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0375, USA.
Robert C SpitaleDepartment of Pharmaceutical Sciences, University of California Irvine, 147 Bison Modular, Building 515, Irvine, CA 92697, USA.
Gourisankar GhoshDepartment of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0375, USA.
University of California San Diego · USUniversity of California, Irvine · US

Funding

Higher Precision Human and Mouse TranscriptomesUM1HG009443 · NHGRI · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI MORTAZAVI, SEYED ALI, WOLD, BARBARA J · 2017 to 2021
$15.5M
Investigation of Gene Regulation by NF-kappaB Transcription factorsR01GM085490 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GHOSH, GOURISANKAR · 2009 to 2023
$3.8M
ASF/SF2: Phosphorylation and RNA BindingR01GM084277 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GHOSH, GOURISANKAR · 2009 to 2012
$1.3M
NHGRI NIH HHS UM1 HG009443NIGMS NIH HHS R01 GM084277NIGMS NIH HHS R01 GM085490
6 · The paper itself

Abstract

Recognition of highly degenerate mammalian splice sites by the core spliceosomal machinery is regulated by several protein factors that predominantly bind exonic splicing motifs. These are postulated to be single-stranded in order to be functional, yet knowledge of secondary structural features that regulate the exposure of exonic splicing motifs across the transcriptome is not currently available. Using transcriptome-wide RNA structural information we show that retained introns in mouse are commonly flanked by a short (≲70 nucleotide), highly base-paired segment upstream and a predominantly single-stranded exonic segment downstream. Splicing assays with select pre-mRNA substrates demonstrate that loops immediately upstream of the introns contain pre-mRNA-specific splicing enhancers, the substitution or hybridization of which impedes splicing. Additionally, the exonic segments flanking the retained introns appeared to be more enriched in a previously identified set of hexameric exonic splicing enhancer (ESE) sequences compared to their spliced counterparts, suggesting that base-pairing in the exonic segments upstream of retained introns could be a means for occlusion of ESEs. The upstream exonic loops of the test substrate promoted recruitment of splicing factors and consequent pre-mRNA structural remodeling, leading up to assembly of the early spliceosome. These results suggest that disruption of exonic stem-loop structures immediately upstream (but not downstream) of the introns regulate alternative splicing events, likely through modulating accessibility of splicing factors.

Indexed as

Base PairingExonsIntronsRNA SplicingAdenoviridaeAnimalsBase Sequencebeta-GlobinsEnhancer Elements, GeneticGene SilencingMiceMouse Embryonic Stem CellsMutationRNA PrecursorsSpliceosomesTranscriptomebeta-GlobinsRNA Precursors

Identifiers

PMID32402057
PMCPMC7293017
OpenAlexW3024286496

What OpenQuestion holds

Textmetadata
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.