Evidence map›Paper›PMID 19147685›Full record

ArticleHuman molecular genetics2009

Tannic acid facilitates expression of the polypyrimidine tract binding protein and alleviates deleterious inclusion of CHRNA1 exon P3A due to an hnRNP H-disrupting mutation in congenital myasthenic syndrome.

Yang Bian, Akio Masuda, Tohru Matsuura, Mikako Ito, Kazuya Okushin, Andrew G Engel, Kinji Ohno

Open access · bronzeAbstract read
In one paragraph

Article in Human molecular genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
0.8field-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

16 citing papers in PubMed, 33 citations in OpenAlex.

  1. Article
  2. Review
  3. Treating pediatric neuromuscular disorders: The future is now.American journal of medical genetics. Part A · 2018
    Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. 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

7 authors at 2 institutions in 2 countries.

Yang BianDivision of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Akio Masuda
Tohru Matsuura
Mikako Ito
Kazuya Okushin
Andrew G Engel
Kinji Ohno
Nagoya University · JPMayo Clinic in Florida · US

Funding

ELECTRON MICROSCOPY OF MYOPATHIESR01NS006277 · NINDS · MAYO CLINIC ROCHESTER · PI ENGEL, ANDREW GEORGE · 1985 to 2015
$7.8M
NINDS NIH HHS NS6277
6 · The paper itself

Abstract

We recently reported that the intronic splice-site mutation IVS3-8G>A of CHRNA1 that encodes the muscle nicotinic acetylcholine receptor alpha subunit disrupts binding of a splicing repressor, hnRNP H. This, in turn, results in exclusive inclusion of the downstream exon P3A. The P3A(+) transcript encodes a non-functional alpha subunit that comprises 50% of the transcripts in normal human skeletal muscle, but its functional significance remains undetermined. In an effort to search for a potential therapy, we screened off-label effects of 960 bioactive chemical compounds and found that tannic acid ameliorates the aberrant splicing due to IVS3-8G>A but without altering the expression of hnRNP H. Therefore, we searched for another splicing trans-factor. We found that the polypyrimidine tract binding protein (PTB) binds close to the 3' end of CHRNA1 intron 3, that PTB induces skipping of exon P3A and that tannic acid increases the expression of PTB in a dose-dependent manner. Deletion assays of the PTB promoter region revealed that the tannic acid-responsive element is between positions -232 and -74 from the translation initiation site. These observations open the door to the discovery of novel therapies based on PTB overexpression and to detecting possible untoward effects of the overexpression.

Indexed as

Base SequenceCell LineDose-Response Relationship, DrugExonsHeterogeneous-Nuclear Ribonucleoprotein Group F-HHeterogeneous-Nuclear RibonucleoproteinsHumansIntronsLuciferasesMolecular Sequence DataMutationMyasthenic Syndromes, CongenitalPolypyrimidine Tract-Binding ProteinPromoter Regions, GeneticProtein BindingReceptors, NicotinicCHRNA1 protein, humanHeterogeneous-Nuclear Ribonucleoprotein Group F-HHeterogeneous-Nuclear RibonucleoproteinsLuciferasesPolypyrimidine Tract-Binding ProteinPTBP1 protein, humanReceptors, NicotinicRNA Splice SitesTannins

Identifiers

PMID19147685
PMCPMC2655771
OpenAlexW2169222490

What OpenQuestion holds

Textmetadata
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.