The Role of N6-Methyladenosine Modified Circular RNA in Pathophysiological Processes

Circular RNA (circRNA) is a type of covalently closed and endogenous non-coding RNA (ncRNA) with tissue- and cell-specific expression patterns generated by a non-canonical splicing event. Previous reports have indicated that circRNAs exert their functions in different ways, thereby participating in various pathophysiological processes. N⁶-methyladenosine (m⁶A) methylation occurs in the N⁶-position, which is the most abundant and conserved internal transcriptional modification in eukaryotes, including mRNA and ncRNAs. Accumulating evidences confirm that m⁶A modification also exists in the circRNA and greatly affects the biological functions of circRNA. Their dysregulated expression can be a cause of various pathophysiological processes, such as spermatogenesis, myoblast differentiation, cancer, cardiovascular disease, mental illness and so on. Understanding the role of m⁶A-modified circRNAs in pathophysiological processes may contribute to better understanding the physiological mechanisms and develop new biomarkers. This review summarizes the regulatory mechanism of m⁶A modification on circRNA metabolism and the role of m⁶A-modified circRNAs in pathophysiological processes. This article may pave the way for a better understanding of the role of epigenetically modified circRNAs in pathophysiological process.