Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • News & Views
  • Published:

Congenital heart disease

How RNA splicing decisions shape and break the developing heart

Nature Cardiovascular Research volume 5, pages 284–285 (2026) Cite this article

Subjects

Splice-altering genetic variants are found in individuals with infantile cardiomyopathy, but the consequences are unclear. A study now shows that aberrant splicing of only one exon in the AARS2 gene can cause devastating heart development defects, phenocopying patient congenital cardiomyopathy.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Schematic of how mis-splicing of AARS2 exon 16 leads to cardiac development defects and cardiomyopathy.
The alternative text for this image may have been generated using AI.

References

  1. Homsy, J. et al. Science 350, 1262–1266 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Awaya, T. et al. J. Hum. Genet. https://doi.org/10.1038/s10038-025-01424-z (2025).

    Article  PubMed  Google Scholar 

  3. Jang, M. Y. et al. Circ. Genom. Precis. Med. 16, 224–231 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Lu, Y. W. et al. Nat. Cardiovasc. Res. https://doi.org/10.1038/s44161-026-00798-3 (2026).

    Article  Google Scholar 

  5. Berget, S. M. et al. Proc. Natl Acad. Sci. USA 74, 3171–3175 (1977).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Chow, L. T. et al. Cell 12, 1–8 (1977).

    Article  CAS  PubMed  Google Scholar 

  7. Rohner, E. et al. Nat. Biotechnol. 40, 1586–1600 (2022).

    Article  CAS  PubMed  Google Scholar 

  8. Wang, E. T. et al. Nature 456, 470–476 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Gerstberger, S. et al. Adv. Exp. Med. Biol. 825, 1–55 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Verma, S. K. et al. Curr. Top. Dev. Biol. 156, 51–119 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Sommerville, E. W. et al. Hum. Mol. Genet. 28, 258–268 (2019).

    PubMed  PubMed Central  Google Scholar 

  12. Szpisjak, L. et al. J. Hum. Genet. 62, 329–333 (2017).

    Article  CAS  PubMed  Google Scholar 

  13. MacGrogan, D. et al. Nat. Rev. Cardiol. 15, 685–704 (2018).

    Article  PubMed  Google Scholar 

  14. Tien, P. C. et al. Oncogene 42, 2521–2535 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ji, X. et al. Mol. Cell. Biol. 41, e0066820 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, VA, USA

    Rachel L. DeLancey, Sunil K. Verma & Muge N. Kuyumcu-Martinez

  2. Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA, USA

    Muge N. Kuyumcu-Martinez

  3. University of Virginia Cancer Center, Charlottesville, VA, USA

    Muge N. Kuyumcu-Martinez

  4. University of Virginia Center for RNA Science and Medicine, Charlottesville, VA, USA

    Muge N. Kuyumcu-Martinez

Authors
  1. Rachel L. DeLancey
    View author publications

    Search author on:PubMed Google Scholar

  2. Sunil K. Verma
    View author publications

    Search author on:PubMed Google Scholar

  3. Muge N. Kuyumcu-Martinez
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Muge N. Kuyumcu-Martinez.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

DeLancey, R.L., Verma, S.K. & Kuyumcu-Martinez, M.N. How RNA splicing decisions shape and break the developing heart. Nat Cardiovasc Res 5, 284–285 (2026). https://doi.org/10.1038/s44161-026-00801-x

Download citation

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s44161-026-00801-x

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing