Abstract
Cardiac development and function are becoming increasingly well understood from different angles, including signalling, transcriptional and epigenetic mechanisms. By contrast, the importance of the post-transcriptional landscape of cardiac biology largely remains to be uncovered, building on the foundation of a few existing paradigms. The discovery during the past decade of hundreds of additional RNA-binding proteins in mammalian cells and organs, including the heart, is expected to accelerate progress and has raised intriguing possibilities for better understanding the intricacies of cardiac development, metabolism and adaptive alterations. In this Review, we discuss the progress and new concepts on RNA-binding proteins and RNA biology and appraise them in the context of common cardiovascular clinical conditions, from cell and organ-wide perspectives. We also discuss how a better understanding of cardiac RNA-binding proteins can fill crucial knowledge gaps in cardiology and might pave the way to developing better treatments to reduce cardiovascular morbidity and mortality.
Key points
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The number of proteins identified to have RNA-binding activity, termed RNA-binding proteins (RBPs), has more than tripled during the past decade, including many proteins with well-annotated cell functions.
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The identified cardiomyocyte-specific RBPome has also expanded profoundly, with numerous proteins that are crucial for cardiac functions having been identified to bind to RNA.
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Similarly to how post-translational modifications can alter protein function, the direct and specific binding of RNA can also regulate protein function — a process called riboregulation.
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Variants in RBPs are increasingly being recognized as a cause of common cardiovascular diseases, and these RBPs have become a focus of targeted therapies.
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Acknowledgements
The authors are grateful to Thomas Schwarzl (EMBL, Germany) for contributing to Fig. 4. The authors receive support from Sonderforschungsbereich 1550 of the Deutsche Forschungsgemeinschaft (to M.V. and M.W.H.), the Boehringer-Ingelheim Stiftung Programm Plus3 (to M.V.), the Australian National Health and Medical Research Council APP1045417 & 1120483 (to T.P. and M.W.H.) and APP1135928 & 2018363 (to T.P.), and the Manfred Lautenschläger Stiftung (to M.W.H.).
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Völkers, M., Preiss, T. & Hentze, M.W. RNA-binding proteins in cardiovascular biology and disease: the beat goes on. Nat Rev Cardiol (2024). https://doi.org/10.1038/s41569-023-00958-z
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DOI: https://doi.org/10.1038/s41569-023-00958-z
