The Role of N(6)-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. N(6)-methyladenosine (m(6)A) methylation occurs in the N(6)-position, which is the most abundant and conserved internal transcriptional modification in eukaryotes, including mRNA and ncRNAs. Accumulating evidences confirm that m(6)A 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 m(6)A-modified circRNAs in pathophysiological processes may contribute to better understanding the physiological mechanisms and develop new biomarkers. This review summarizes the regulatory mechanism of m(6)A modification on circRNA metabolism and the role of m(6)A-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.