Epitranscriptomics in the Heart: a Focus on m 6 A
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TRANSLATIONAL RESEARCH IN HEART FAILURE (J BACKS & M VAN DEN HOOGENHOF, SECTION EDITORS)
Epitranscriptomics in the Heart: a Focus on m6A Jacob Z. Longenecker 1 & Christopher J. Gilbert 1 & Volha A. Golubeva 1 & Colton R. Martens 1 & Federica Accornero 1
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose of Review Post-transcriptional modifications are key regulators of gene expression that allow the cell to respond to environmental stimuli. The most abundant internal mRNA modification is N6-methyladenosine (m6A), which has been shown to be involved in the regulation of RNA splicing, localization, translation, and decay. It has also been implicated in a wide range of diseases, and here, we review recent evidence of m6A’s involvement in cardiac pathologies and processes. Recent Findings Studies have primarily relied on gain and loss of function models for the enzymes responsible for adding and removing the m6A modification. Results have revealed a multifaceted role for m6A in the heart’s response to myocardial infarction, pressure overload, and ischemia/reperfusion injuries. Genome-wide analyses of mRNAs that are differentially methylated during cardiac stress have highlighted the importance of m6A in regulating the translation of specific categories of transcripts implicated in pathways such as calcium handling, cell growth, autophagy, and adrenergic signaling in cardiomyocytes. Summary Regulation of gene expression by m6A is critical for cardiomyocyte homeostasis and stress responses, suggesting a key role for this modification in cardiac pathophysiology. Keywords Heart failure . m6A . RNA methylation . Epigenetics
Abbreviations m6A N6-Methyladenosine METTL3 Methyltransferase like-3 FTO Fat mass and obesity–related protein ALKBH5 AlkB Homolog 5 YTHDF1 YT521-B Homology domain family protein 1 YTHDF2 YT521-B Homology domain family protein 2 YTHDF3 YT521-B Homology domain family protein 3
Introduction Regulation of cardiac-specific genes plays an important role during normal heart development as well as throughout This article is part of Topical Collection on Translational Research in Heart Failure * Federica Accornero [email protected] 1
Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, 473 W 12th Ave, Columbus, OH 43210, USA
adulthood when the myocardium undergoes age-related remodeling. Moreover, changes in gene expression in response to stress or injury are also key to understanding cardiac pathology. The journey to making a functional gene product consists of multiple fundamental steps, all of which are impeccably coordinated by sophisticated regulatory mechanisms. At the epigenomic level, chromatin remodeling and chemical modifications on DNA can regulate the expression of genes important for cardiogenesis and cardiomyocyte stress responses [1, 2]. Several systematic studies have highlighted the contribution of DNA methylation, histone modifiers, transcription factors, and long non-coding
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