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Updated: Jan 26, 2026
Correlating Gene-specific DNA Methylation Changes with Expression and Transcriptional Activity of Astrocytic KCNJ10 Kir4.1
Published on: September 26, 2015
m6A-mRNA methylation regulates cardiac gene expression and cellular growth
Vivien Kmietczyk1,2, Eva Riechert1,2, Laura Kalinski1,2
1Department of Cardiology, Angiology, and Pneumology, University Hospital Heidelberg, University of Heidelberg, Heidelberg, Germany.
Abstract:
Conceptually similar to modifications of DNA, mRNAs undergo chemical modifications, which can affect their activity, localization, and stability. The most prevalent internal modification in mRNA is the methylation of adenosine at the N6-position (m6A). This returns mRNA to a role as a central hub of information within the cell, serving as an information carrier, modifier, and attenuator for many biological processes. Still, the precise role of internal mRNA modifications such as m6A in human and murine-dilated cardiac tissue remains unknown. Transcriptome-wide mapping of m6A in mRNA allowed us to catalog m6A targets in human and murine hearts. Increased m6A methylation was found in human cardiomyopathy. Knockdown and overexpression of the m6A writer enzyme Mettl3 affected cell size and cellular remodeling both in vitro and in vivo. Our data suggest that mRNA methylation is highly dynamic in cardiomyocytes undergoing stress and that changes in the mRNA methylome regulate translational efficiency by affecting transcript stability. Once elucidated, manipulations of methylation of specific m6A sites could be a powerful approach to prevent worsening of cardiac function.
Insights
Messenger RNA (mRNA) methylation, N6-methyladenosine (m6A), impacts cell size and cardiac remodeling. Changes in m6A levels in heart tissue may offer new therapeutic targets for cardiomyopathy.
Area of Science:
- Molecular Biology
- Epigenetics
- Cardiovascular Research
Background:
- Messenger RNAs (mRNAs) undergo chemical modifications, influencing their function.
- N6-methyladenosine (m6A) is the most prevalent internal mRNA modification, affecting gene expression.
- The role of m6A in cardiac tissue, particularly in dilated cardiomyopathy, is not well understood.
Purpose of the Study:
- To investigate the role and impact of m6A in human and murine cardiac tissue.
- To identify m6A targets in the heart and their association with cardiomyopathy.
- To explore the functional consequences of altering m6A levels in cardiomyocytes.
Main Methods:
- Transcriptome-wide mapping of m6A in mRNA from human and murine hearts.
- In vitro and in vivo studies involving knockdown and overexpression of the m6A writer enzyme Mettl3.
- Analysis of cell size and cellular remodeling in response to Mettl3 manipulation.
Main Results:
- Cataloged m6A targets in human and murine hearts.
- Observed increased m6A methylation in human cardiomyopathy.
- Demonstrated that Mettl3 manipulation affects cardiomyocyte size and remodeling.
- Showed mRNA methylation is dynamic in stressed cardiomyocytes, regulating translational efficiency via transcript stability.
Conclusions:
- mRNA methylation (m6A) is a dynamic process in cardiomyocytes, particularly under stress.
- Altered m6A levels are associated with human cardiomyopathy and affect cardiac cell function.
- Targeting specific m6A sites presents a potential therapeutic strategy for improving cardiac function.
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