Evidence map›Paper›PMID 25263560›Full record

ArticleCell reports2014

A targeted oligonucleotide enhancer of SMN2 exon 7 splicing forms competing quadruplex and protein complexes in functional conditions.

Lindsay D Smith, Rachel L Dickinson, Christian M Lucas, Alex Cousins, Alexey A Malygin, Carika Weldon, Andrew J Perrett, Andrew R Bottrill, Mark S Searle, Glenn A Burley and 1 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
0.9field-weighted citation impact, top 27% 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

13 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
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

11 authors at 4 institutions in 2 countries.

Lindsay D SmithDepartment of Biochemistry, University of Leicester, Leicester LE1 9HN, UK.
Rachel L DickinsonDepartment of Biochemistry, University of Leicester, Leicester LE1 9HN, UK; Department of Chemistry, University of Leicester, Leicester LE1 7RH, UK.
Christian M LucasDepartment of Biochemistry, University of Leicester, Leicester LE1 9HN, UK.
Alex CousinsSchool of Chemistry, Centre for Biomolecular Sciences, University of Nottingham, Nottingham NG7 2RD, UK.
Alexey A MalyginInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, Russia.
Carika WeldonDepartment of Biochemistry, University of Leicester, Leicester LE1 9HN, UK.
Andrew J PerrettDepartment of Chemistry, University of Leicester, Leicester LE1 7RH, UK.
Andrew R BottrillProtein and Nucleic Acid Chemistry Laboratory, University of Leicester, Leicester LE1 9HN, UK.
Mark S SearleSchool of Chemistry, Centre for Biomolecular Sciences, University of Nottingham, Nottingham NG7 2RD, UK.
Glenn A BurleyDepartment of Pure & Applied Chemistry, University of Strathclyde, Glasgow G1 1XL, UK. Electronic address: glenn.burley@strath.ac.uk.
Ian C EperonDepartment of Biochemistry, University of Leicester, Leicester LE1 9HN, UK. Electronic address: eci@leicester.ac.uk.
University of Leicester · GBUniversity of Nottingham · GBInstitute of Chemical Biology and Fundamental Medicine · RUUniversity of Strathclyde · GB

Funding

Medical Research Council
6 · The paper itself

Abstract

The use of oligonucleotides to activate the splicing of selected exons is limited by a poor understanding of the mechanisms affected. A targeted bifunctional oligonucleotide enhancer of splicing (TOES) anneals to SMN2 exon 7 and carries an exonic splicing enhancer (ESE) sequence. We show that it stimulates splicing specifically of intron 6 in the presence of repressing sequences in intron 7. Complementarity to the 5' end of exon 7 increases U2AF65 binding, but the ESE sequence is required for efficient recruitment of U2 snRNP. The ESE forms at least three coexisting discrete states: a quadruplex, a complex containing only hnRNP F/H, and a complex enriched in the activator SRSF1. Neither hnRNP H nor quadruplex formation contributes to ESE activity. The results suggest that splicing limited by weak signals can be rescued by rapid exchange of TOES oligonucleotides in various complexes and raise the possibility that SR proteins associate transiently with ESEs.

Indexed as

ExonsBase SequenceHumansIntronsNuclear ProteinsOligonucleotidesRibonucleoproteinsRibonucleoprotein, U2 Small NuclearRNA Splice SitesRNA SplicingSpliceosomesSplicing Factor U2AFSurvival of Motor Neuron 2 ProteinNuclear ProteinsOligonucleotidesRibonucleoproteinsRibonucleoprotein, U2 Small NuclearRNA Splice SitesSMN2 protein, humanSplicing Factor U2AFSurvival of Motor Neuron 2 ProteinU2AF2 protein, human

Identifiers

PMID25263560
PMCPMC4536295
OpenAlexW2041811354

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.