Evidence map›Paper›PMID 21724598›Full record

ArticleNucleic acids research2011

Molecular design of a splicing switch responsive to the RNA binding protein Tra2β.

Sushma Nagaraja Grellscheid, Caroline Dalgliesh, Agata Rozanska, David Grellscheid, Cyril F Bourgeois, James Stévenin, David J Elliott

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.3field-weighted citation impact, top 21% 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

19 citing papers in PubMed, 23 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. 3'untranslated regions (3'UTR) ofAmerican journal of cancer research · 2021
    Article
  6. Article
  7. Article
  8. Article
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  10. Review
  11. Prognostic value of transformer 2β expression in prostate cancer.International journal of clinical and experimental pathology · 2015
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
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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

7 authors at 5 institutions in 2 countries.

Sushma Nagaraja GrellscheidInstitute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, NE1 3BZ, UK.
Caroline Dalgliesh
Agata Rozanska
David Grellscheid
Cyril F Bourgeois
James Stévenin
David J Elliott
Centre National de la Recherche Scientifique · FRInstitut de génétique et de biologie moléculaire et cellulaire · FRInserm · FRNewcastle University · GBUniversité de Strasbourg · FR

Funding

Biotechnology and Biological Sciences Research Council BB/D013917/1Wellcome Trust WT080368MA
6 · The paper itself

Abstract

Tra2β regulates a number of splicing switches including activation of the human testis-specific exon HIPK3-T in the Homeodomain Interacting Protein Kinase 3 gene. By testing HIPK3-T exons of different intrinsic strengths, we found Tra2β most efficiently activated splicing inclusion of intrinsically weak exons, although these were spliced at a lower overall level. Both the RRM and N-terminal RS-rich region of Tra2β were required for splicing activation. Bioinformatic searches for splicing enhancers and repressors mapped four physically distinct exonic splicing enhancers (ESEs) within HIPK3-T, each containing the known Tra2β AGAA-rich binding site. Surprisingly disruption of each single ESE prevented Tra2β-mediated activation, although single mutated exons could still bind Tra2β protein by gel shifts and functional splicing analyses. Titration experiments indicate an additive model of HIPK3-T splicing activation, requiring availability of an array of four distinct ESEs to enable splicing activation. To enable this efficient Tra2β-mediated splicing switch to operate, a closely adjacent downstream and potentially competitive stronger 5'-splice site is actively repressed. Our data indicate that a novel arrangement of multiple mono-specific AGAA-rich ESEs coupled to a weak 5'-splice site functions as a responsive gauge. This gauge monitors changes in the specific nuclear concentration of the RNA binding protein Tra2β, and co-ordinately regulates HIPK3-T exon splicing inclusion.

Indexed as

Alternative SplicingRegulatory Sequences, Ribonucleic AcidExonsHumansIntracellular Signaling Peptides and ProteinsNerve Tissue ProteinsProtein Serine-Threonine KinasesProtein Structure, TertiaryRNA-Binding ProteinsRNA Splice SitesSerine-Arginine Splicing FactorsHIPK3 protein, humanIntracellular Signaling Peptides and ProteinsNerve Tissue ProteinsProtein Serine-Threonine KinasesRegulatory Sequences, Ribonucleic AcidRNA-Binding ProteinsRNA Splice SitesSerine-Arginine Splicing FactorsTRA2B protein, human

Identifiers

PMID21724598
PMCPMC3185414
OpenAlexW1994924520

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.