Evidence map›Paper›PMID 33300159›Full record

ArticleHuman mutation2021

Identification of SRSF10 as a regulator of SMN2 ISS-N1.

Sabrina B Frederiksen, Lise L Holm, Martin R Larsen, Thomas K Doktor, Henriette S Andersen, Michelle L Hastings, Yimin Hua, Adrian R Krainer, Brage S Andresen

Open access · bronzeAbstract read
In one paragraph

Article in Human mutation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.2field-weighted citation impact, top 22% 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

10 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. Article
  3. RegulatingMolecular therapy. Nucleic acids · 2024
    Article
  4. Article
  5. Article
  6. Gene Therapy in ALS and SMA: Advances, Challenges and Perspectives.International journal of molecular sciences · 2023
    Review
  7. Article
  8. Review
  9. Review
  10. 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

9 authors at 3 institutions in 2 countries.

Sabrina B FrederiksenDepartment of Biochemistry and Molecular Biology and the Villum Center for Bioanalytical Sciences, University of Southern Denmark, Odense M, Denmark.
Lise L HolmDepartment of Biochemistry and Molecular Biology and the Villum Center for Bioanalytical Sciences, University of Southern Denmark, Odense M, Denmark.
Martin R LarsenDepartment of Biochemistry and Molecular Biology and the Villum Center for Bioanalytical Sciences, University of Southern Denmark, Odense M, Denmark.
Thomas K DoktorDepartment of Biochemistry and Molecular Biology and the Villum Center for Bioanalytical Sciences, University of Southern Denmark, Odense M, Denmark.
Henriette S AndersenDepartment of Biochemistry and Molecular Biology and the Villum Center for Bioanalytical Sciences, University of Southern Denmark, Odense M, Denmark.
Michelle L HastingsDepartment of Cell Biology and Anatomy, Center for Genetic Diseases, Chicago Medical School and School of Graduate and Postdoctoral Studies, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, USA.
Yimin HuaCold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.
Adrian R KrainerCold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.
Brage S AndresenDepartment of Biochemistry and Molecular Biology and the Villum Center for Bioanalytical Sciences, University of Southern Denmark, Odense M, Denmark.ORCID 0000-0001-7488-3035
University of Southern Denmark · DKCold Spring Harbor Laboratory · USRosalind Franklin University of Medicine and Science · US

Funding

Single-Cell Biology Shared ResourceP30CA045508 · NCI · COLD SPRING HARBOR LABORATORY · PI John Edward Moses · 1987 to 2026
$118.9M
BIOCHEMISTRY OF PREMRNA SPLICINGR01GM042699 · NIGMS · COLD SPRING HARBOR LABORATORY · PI Adrian R Krainer · 1989 to 2026
$8.8M
Biochemistry of Pre-mRNA SplicingR37GM042699 · NIGMS · COLD SPRING HARBOR LABORATORY · PI KRAINER, ADRIAN R · 2012 to 2021
$7.7M
NCI NIH HHS P30 CA045508NIGMS NIH HHS R01 GM042699NIGMS NIH HHS R37 GM042699
6 · The paper itself

Abstract

Understanding the splicing code can be challenging as several splicing factors bind to many splicing-regulatory elements. The SMN1 and SMN2 silencer element ISS-N1 is the target of the antisense oligonucleotide drug, Spinraza, which is the treatment against spinal muscular atrophy. However, limited knowledge about the nature of the splicing factors that bind to ISS-N1 and inhibit splicing exists. It is likely that the effect of Spinraza comes from blocking binding of these factors, but so far, an unbiased characterization has not been performed and only members of the hnRNP A1/A2 family have been identified by Western blot analysis and nuclear magnetic resonance to bind to this silencer. Employing an MS/MS-based approach and surface plasmon resonance imaging, we show for the first time that splicing factor SRSF10 binds to ISS-N1. Furthermore, using splice-switching oligonucleotides we modulated the splicing of the SRSF10 isoforms generating either the long or the short protein isoform of SRSF10 to regulate endogenous SMN2 exon 7 inclusion. We demonstrate that the isoforms of SRSF10 regulate SMN1 and SMN2 splicing with different strength correlating with the length of their RS domain. Our results suggest that the ratio between the SRSF10 isoforms is important for splicing regulation.

Indexed as

Cell Cycle ProteinsMuscular Atrophy, SpinalRepressor ProteinsSerine-Arginine Splicing FactorsSurvival of Motor Neuron 2 ProteinExonsHumansOligonucleotides, AntisenseRNA SplicingTandem Mass SpectrometryCell Cycle ProteinsOligonucleotides, AntisenseRepressor ProteinsSerine-Arginine Splicing FactorsSMN2 protein, humanSRSF10 protein, humanSurvival of Motor Neuron 2 Proteinalternative splicingantisense oligonucleotidesSMN2spinal muscular atrophySRSF10

Identifiers

PMID33300159
PMCPMC7878440
OpenAlexW3111486716

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.