Purpose of review Gene expression is regulated at multiple levels beyond genetic and epigenetic modifications of DNA. Even when DNA is accurately transcribed into RNA, transcript abundance often does not correlate with protein levels, underscoring the importance of posttranscriptional regulation. Chemical modifications of RNA occur in both coding and noncoding RNAs and add an additional layer of gene control. More than 170 distinct RNA modifications have been identified across different RNAs in all domains of life. Although the abundant modifications have been investigated, their roles in cardiac biology and heart failure remain incompletely defined. This review discusses the current knowledge of both well characterized and understudied RNA modifications in the heart. Recent findings Recent studies highlight context-dependent roles of N6-methyladenosine (m 6 A), 5-methylcytosine (m 5 C), N4-acetylcytidine (ac 4 C), and adenosine-to-inosine (A-to-I) RNA editing in the heart are discussed in this review. Summary RNA modifications constitute a critical regulatory layer that complements transcriptional control and facilitates rapid adaptation to cardiac stress. Dysregulation of m 6 A, m 5 C, and A-to-I editing contributes to pathological remodeling and disease progression. However, most RNA modifications remain unexplored in heart failure. Enzymes that write, erase, or read these marks represent promising targets for precision therapeutic strategies.
Manisha Deogharia (2026) studied this question.