A previously unknown gene was identified for the first time in humans, which plays a crucial role in the maturation of cardiomyocytes, the cells responsible for cardiac contraction. The discovery was made by a research group from the Charles Darwin Department of Biology and Biotechnology at Sapienza University of Rome, in collaboration with the Institute of Molecular Biology and Pathology of the National Research Council (CNR-IBPM) in Rome. The discovery was published in the journal Nature Communications.

The study revealed that the malfunctioning of this gene, named HSCHARME, is associated with cardiomyopathies in different patient cohorts, opening up new prospects for more accurate diagnoses and targeted therapies.

‘This gene belongs to the category of so-called long non-coding RNAs (lncRNAs), molecules that do not give rise to proteins but finely regulate the activity of other genes,’ says Professor Monica Ballarino of Sapienza University of Rome. ‘HSCHARME acts as a true “architect” of the genome, guiding the correct activity of the heart's genes. HSCHARME has proven to be crucial in guiding the development and maturation of cardiomyocytes, the muscle cells responsible for cardiac contraction. When this gene does not function properly, the cells do not develop adequately, with consequences for the health of the entire organ.’

‘The study showed for the first time that HSCHARME controls a fundamental process called “alternative splicing”, which allows individual genes to produce different proteins to ensure the complexity necessary for cells to function properly,’ continues Pietro Laneve of CNR-IBPM. ‘In patients with hypertrophic and dilated cardiomyopathy, two serious and widespread diseases, the function of HSCHARME is altered, with negative effects on cardiac genes and the heart. This makes the gene a potential target for new early diagnosis and personalised therapies.’

This result was made possible thanks to a combination of cutting-edge technologies, from comparative genomics to single-cell transcriptomics, genome editing and the use of induced pluripotent stem cells differentiated into human cardiomyocytes. Using these tools, the researchers reconstructed the gene's molecular partners and studied their function in cell models and clinical samples, identifying the PTBP1 protein as a key cofactor.

This discovery goes beyond basic research: heart disease affects millions of people worldwide and, despite advances in genetics, it remains difficult to predict its progression. Studies such as this open up new prospects for precision medicine capable of identifying individuals at greatest risk and guiding personalised therapies, with the aim of preventing tragic events such as sudden cardiac death.

The Italian Institute of Technology (IIT) also collaborated on the study.

References:

Buonaiuto G, Desideri F, Setti A, Palma A, D'Angelo A, Storari G, Santini T, Laneve P, Trisciuoglio D, Ballarino M. LncRNA HSCHARME is altered in human cardiomyopathies and promotes stem cell-derived cardiomyogenesis via splicing regulation. Nat Commun. 2025 Aug 23;16(1):7880. doi: 10.1038/s41467-025-62754-2. PMID: 40849301. 
https://rdcu.be/eB3Fr

Further Information
Monica Ballarino - Department of Biology and Biotechnology ‘Charles Darwin’ 
monica.ballarino@uniroma1.it