Evidence map›Paper›PMID 35913515›Full record

ArticleCellular and molecular life sciences : CMLS2022

Myocardin regulates exon usage in smooth muscle cells through induction of splicing regulatory factors.

Li Liu, Dmytro Kryvokhyzha, Catarina Rippe, Aishwarya Jacob, Andrea Borreguero-Muñoz, Karin G Stenkula, Ola Hansson, Christopher W J Smith, Steven A Fisher, Karl Swärd

Open access · hybridAbstract read
In one paragraph

Article in Cellular and molecular life sciences : CMLS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
2.0field-weighted citation impact, top 13% 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

17 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. 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
  5. Article
  6. Engineering a serum response factor superactivator of smooth muscle gene expression with a condensate-forming domain.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  7. Article
  8. Review
  9. 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
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. 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

10 authors at 4 institutions in 5 countries.

Li Liu *Department of Experimental Medical Science, BMC D12, SE-22184, Lund, Sweden.
Dmytro Kryvokhyzha *Department of Clinical Sciences, Lund University Diabetes Centre, CRC, 21428, Malmö, Sweden.
Catarina RippeDepartment of Experimental Medical Science, BMC D12, SE-22184, Lund, Sweden.
Aishwarya JacobDepartment of Biochemistry, University of Cambridge, Cambridge, UK.
Andrea Borreguero-MuñozDepartment of Experimental Medical Science, BMC D12, SE-22184, Lund, Sweden.
Karin G StenkulaDepartment of Experimental Medical Science, BMC D12, SE-22184, Lund, Sweden.
Ola HanssonDepartment of Clinical Sciences, Lund University Diabetes Centre, CRC, 21428, Malmö, Sweden.
Christopher W J SmithDepartment of Biochemistry, University of Cambridge, Cambridge, UK.
Steven A FisherDepartment of Medicine (Cardiology) and Physiology and Biophysics, University of Maryland-Baltimore, Baltimore, MD, 21201, USA.
Karl SwärdDepartment of Experimental Medical Science, BMC D12, SE-22184, Lund, Sweden. karl.sward@med.lu.se.ORCID http://orcid.org/0000-0002-7255-5510
Lund University · SEUniversity of Cambridge · GBThird Affiliated Hospital of Guangzhou Medical University · CNUniversity of Maryland, Baltimore · US

Funding

Precision Editing of Myosin Phosphatase for Vasodilator Sensitization in HypertensionR01HL142971 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI FISHER, STEVEN A. · 2019 to 2022
$1.4M
Precision Editing of Myosin Phosphatase as a Novel Approach for Vasodilator Sensitization and Lowering of Blood Pressure in HypertensionI01BX004443 · VA · BALTIMORE VA MEDICAL CENTER · PI FISHER, STEVEN A. · 2019 to 2022
–
BLRD VA I01 BX004443Hjärt-Lungfonden 20200222Kungliga Fysiografiska Sällskapet i Lund F 2022/207NHLBI NIH HHS R01 HL142971NIH HHS R01 HL142971-A1VA MERIT award BX004443VR 2018-02635VR 2020-00908Wellcome TrustWellcome Trust 209368/Z/17/Z
6 · The paper itself

Abstract

Differentiation of smooth muscle cells (SMCs) depends on serum response factor (SRF) and its co-activator myocardin (MYOCD). The role of MYOCD for the SMC program of gene transcription is well established. In contrast, the role of MYOCD in control of SMC-specific alternative exon usage, including exon splicing, has not been explored. In the current work we identified four splicing factors (MBNL1, RBPMS, RBPMS2, and RBFOX2) that correlate with MYOCD across human SMC tissues. Forced expression of MYOCD family members in human coronary artery SMCs in vitro upregulated expression of these splicing factors. For global profiling of transcript diversity, we performed RNA-sequencing after MYOCD transduction. We analyzed alternative transcripts with three different methods. Exon-based analysis identified 1637 features with differential exon usage. For example, usage of 3´ exons in MYLK that encode telokin increased relative to 5´ exons, as did the 17 kDa telokin to 130 kDa MYLK protein ratio. Dedicated event-based analysis identified 239 MYOCD-driven splicing events. Events involving MBNL1, MCAM, and ACTN1 were among the most prominent, and this was confirmed using variant-specific PCR analyses. In support of a role for RBPMS and RBFOX2 in MYOCD-driven splicing we found enrichment of their binding motifs around differentially spliced exons. Moreover, knockdown of either RBPMS or RBFOX2 antagonized splicing events stimulated by MYOCD, including those involving ACTN1, VCL, and MBNL1. Supporting an in vivo role of MYOCD-SRF-driven splicing, we demonstrate altered Rbpms expression and splicing in inducible and SMC-specific Srf knockout mice. We conclude that MYOCD-SRF, in part via RBPMS and RBFOX2, induce a program of differential exon usage and alternative splicing as part of the broader program of SMC differentiation.

Indexed as

Alternative SplicingMyocytes, Smooth MuscleAnimalsCell DifferentiationExonsHumansMiceMyocardinNuclear ProteinsRepressor ProteinsRNA Splicing FactorsTrans-ActivatorsMyocardinNuclear ProteinsRBFOX2 protein, humanRbfox2 protein, mouseRepressor ProteinsRNA Splicing FactorsTrans-ActivatorsActin-bindingDifferentiationFocal adhesionHeartSplicing code

Identifiers

PMID35913515
PMCPMC9343278
OpenAlexW4289169395

What Socratic 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 Socratic graph.