Evidence map›Paper›PMID 27317697›Full record

ArticleNucleic acids research2016

The alternative splicing program of differentiated smooth muscle cells involves concerted non-productive splicing of post-transcriptional regulators.

Miriam Llorian, Clare Gooding, Nicolas Bellora, Martina Hallegger, Adrian Buckroyd, Xiao Wang, Dipen Rajgor, Melis Kayikci, Jack Feltham, Jernej Ule and 2 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
3.0field-weighted citation impact, top 9% 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

43 citing papers in PubMed, 61 citations in OpenAlex.

  1. Article
  2. Review
  3. MBNL loss of function in smooth muscle as a model for myotonic dystrophy associated gastrointestinal dysmotility.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  4. Ultra-Conserved Poison Exons Enable Rapid and Safe Splicing Factor Gene Expression Switches: A Hypothesis.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025
    Review
  5. Article
  6. Article
  7. Article
  8. The RNA-binding protein RBPMS inhibits smooth muscle cell-driven vascular remodeling in atherosclerosis and vascular injury.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  9. Article
  10. Differentiation and Growth-Arrest-Related lncRNA (International journal of molecular sciences · 2024
    Article
  11. Article
  12. Article
  13. RNA binding proteins in cardiovascular development and disease.Current topics in developmental biology · 2024
    Article
  14. Article
  15. Article
  16. Article
  17. Unleashing the potential of catalytic RNAs to combat mis-spliced transcripts.Frontiers in bioengineering and biotechnology · 2023
    Review
  18. 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

12 authors at 5 institutions in 3 countries.

Miriam LlorianDepartment of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK.
Clare GoodingDepartment of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK.
Nicolas BelloraDepartment of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK Catalan Institute for Research and Advanced Studies (ICREA), E08010 Barcelona, Spain.
Martina HalleggerDepartment of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK Computational Genomics, Universitat Pompeu Fabra, E08003 Barcelona, Spain.
Adrian BuckroydDepartment of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK.
Xiao WangDepartment of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK.
Dipen RajgorDepartment of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK.
Melis KayikciINIBIOMA, CONICET-UNComahue, Bariloche 8400 Río Negro, Argentina.
Jack FelthamDepartment of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK.
Jernej UleComputational Genomics, Universitat Pompeu Fabra, E08003 Barcelona, Spain.
Eduardo EyrasDepartment of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK MRC-Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Christopher W J SmithDepartment of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK cwjs1@cam.ac.uk.
University of Cambridge · GBPompeu Fabra University · ESConsejo Nacional de Investigaciones Científicas y Técnicas · ARInstitució Catalana de Recerca i Estudis Avançats · ESMRC Laboratory of Molecular Biology · GB

Funding

British Heart Foundation FS/11/85/29129
6 · The paper itself

Abstract

Alternative splicing (AS) is a key component of gene expression programs that drive cellular differentiation. Smooth muscle cells (SMCs) are important in the function of a number of physiological systems; however, investigation of SMC AS has been restricted to a handful of events. We profiled transcriptome changes in mouse de-differentiating SMCs and observed changes in hundreds of AS events. Exons included in differentiated cells were characterized by particularly weak splice sites and by upstream binding sites for Polypyrimidine Tract Binding protein (PTBP1). Consistent with this, knockdown experiments showed that that PTBP1 represses many smooth muscle specific exons. We also observed coordinated splicing changes predicted to downregulate the expression of core components of U1 and U2 snRNPs, splicing regulators and other post-transcriptional factors in differentiated cells. The levels of cognate proteins were lower or similar in differentiated compared to undifferentiated cells. However, levels of snRNAs did not follow the expression of splicing proteins, and in the case of U1 snRNP we saw reciprocal changes in the levels of U1 snRNA and U1 snRNP proteins. Our results suggest that the AS program in differentiated SMCs is orchestrated by the combined influence of auxiliary RNA binding proteins, such as PTBP1, along with altered activity and stoichiometry of the core splicing machinery.

Indexed as

Alternative SplicingRNA Processing, Post-TranscriptionalAnimalsCell DifferentiationCell LineCells, CulturedExonsGene Expression ProfilingIntronsMiceMyocytes, Smooth MuscleNucleotide MotifsRatsRNA, Small NuclearRNA Splicing FactorsRNA StabilityRNA, Small NuclearRNA Splicing Factors

Identifiers

PMID27317697
PMCPMC5062968
OpenAlexW2429374768

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.