Integration of cellular responses to extracellular cues is essential for cell survival and adaptation to stress. Extracellular signal-regulated kinase (ERK) 1 and 2 serve an evolutionarily conserved role for intracellular signal transduction that proved critical for cardiomyocyte homeostasis and cardiac stress responses. Considering the importance of ERK1/2 in the heart, understanding how these kinases operate in both normal and disease states is critical. Here, we review the complexity of upstream and downstream signals that govern ERK1/2-dependent regulation of cardiac structure and function. Particular emphasis is given to cardiomyocyte hypertrophy as an outcome of ERK1/2 activation regulation in the heart.

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 (m 6 A), 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 m 6 A'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 m 6 A modification. Results have revealed a multifaceted role for m 6 A 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 m 6 A 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 m 6 A is critical for cardiomyocyte homeostasis and stress responses, suggesting a key role for this modification in cardiac pathophysiology.

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