Regulation of gene expression plays a fundamental role in cardiac stress-responses. Modification of coding transcripts by adenosine methylation (m⁶A) has recently emerged as a critical post-transcriptional mechanism underlying heart disease. Thousands of mammalian mRNAs are known to be m⁶A-modified, suggesting that remodeling of the m⁶A landscape may play an important role in cardiac pathophysiology. Here we found an increase in m⁶A content in human heart failure samples. We then adopted genome-wide analysis to define all m⁶A-regulated sites in human failing compared to non-failing hearts and identified targeted transcripts involved in histone modification as enriched in heart failure. Further, we compared all m⁶A sites regulated in human hearts with the ones occurring in isolated rat hypertrophic cardiomyocytes to define cardiomyocyte-specific m⁶A events conserved across species. Our results identified 38 shared transcripts targeted by m⁶A during stress conditions, and 11 events that are unique to unstressed cardiomyocytes. Of these, further evaluation of select mRNA and protein abundances demonstrates the potential impact of m⁶A on post-transcriptional regulation of gene expression in the heart.

基因表达的调节在心脏应激反应中起重要作用。^{通过腺苷甲基化 (m 6} A)修饰编码转录本最近已成为心脏病的关键转录后机制。已知数以千计的哺乳动物 mRNA 是 m ⁶ A 修饰的，这表明 m ⁶ A 景观的重塑可能在心脏病理生理学中起重要作用。在这里，我们发现人类心力衰竭样本中的 m ⁶ A 含量增加。然后我们采用全基因组分析来定义所有 m ⁶与非衰竭心脏相比，人类衰竭中的 A 调节位点和确定的参与组蛋白修饰的靶向转录物富含心力衰竭。此外，我们将人类心脏中调节的所有 m ⁶ A 位点与分离的大鼠肥大心肌细胞中发生的位点进行比较，以确定跨物种保守的心肌细胞特异性 m ^{6 A 事件。我们的结果确定了在压力条件下 m 6} A靶向的 38 个共享转录本，以及 11 个无压力心肌细胞特有的事件。其中，对选定的 mRNA 和蛋白质丰度的进一步评估证明了 m ⁶ A 对心脏基因表达的转录后调控的潜在影响。