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

Abstract

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.

N6-Methyladenosine in Cancer Immunotherapy: An Undervalued Therapeutic Target

“…In addition, m 6 A modification on circRNA has been identified and characterized (62). Furthermore, m 6 A modifications are believed to be involved in the biogenesis, translation, export and endoribonucleolytic cleavage of circRNAs, which has been discussed (63).…”

Novel insight of N6-methyladenosine modified subtypes in abdominal aortic aneurysm

“…Since individual m6Ascore for patients were calculated based on the m6A related signature, the alteration of the expression profile could change the m6Ascore. Mounting evidence implies that circRNAs play an important role in regulating gene expression by directly binding to proteins ( Huang et al, 2020a ; Okholm et al, 2020 ; Zhou et al, 2020 ) and participating in m6A methylation modifications by interacting with m6A regulators ( Chen et al, 2021 ; Tang and Lv, 2021 ; Issah et al, 2022 ). Therefore, the potential circRNAs that might affect the m6A related signature were identified using a cutoff value of |log2FC| ≥ 2 and p -value <0.05.…”

Microarray and bioinformatic analysis reveal the parental genes of m6A modified circRNAs as novel prognostic signatures in colorectal cancer

“…In addition, growing evidence reveals that circRNAs contribute to various physiological and pathological processes, including the initiation and progression of cancer (31). It is worth noting that m6A modification also exists in the circRNAs and greatly affects the biological functions of circRNAs (32). Interestingly, some circRNAs located in the nucleus can regulate the transcription of the parental gene by binding to RNA polymerase II (33).…”