Epigenetics in Neurodevelopment: Emerging Role of Circular RNA

Abstract

Canonical epigenetic modifications, including DNA methylation, histone modification and chromatin remodeling, play a role in numerous life processes, particularly neurodevelopment. Epigenetics explains the development of cells in an organism with the same DNA sequence into different cell types with various functions. However, previous studies on epigenetics have only focused on the chromatin level. Recently, epigenetic modifications of RNA, which mainly include 6-methyladenosine (m 6 A), pseudouridine, 5-methylcytidine (m 5 C), inosine (I), 2′- O -ribosemethylation, and 1-methyladenosine (m 1 A), have gained increasing attention. Circular RNAs (circRNAs), which are a type of non-coding RNA without a 5′ cap or 3′ poly (A) tail, are abundantly found in the brain and might respond to and regulate synaptic function. Also, circRNAs have various functions, such as microRNA sponge, regulation of gene transcription and interaction with RNA binding protein. In addition, circRNAs are methylated by N 6 -methyladenosine (m 6 A). In this review, we discuss the crucial roles of epigenetic modifications of circRNAs, such as m 6 A, in the genesis and development of neurons and in synaptic function and plasticity. Thus, this type of changes in circRNAs might be a therapeutic target in central nervous system (CNS) disorders and could aid the diagnosis and treatment of these disorders.

Functions and clinical significance of circular RNAs in glioma

“…Considerable evidence verified that RNA epigenetic modifications play a vital role in CNS diseases, including glioma. It is demonstrated that m6A modification induced highly cell-specific expression, and m6A circRNAs have long single exons [151]. Park et al revealed that m6A recognized the binding of the protein YTHDF2 to the target molecule and recruited HRSP12 to mediate the cleavage of circRNA by the RNA endonuclease RNase P/MRP complex, suggesting critical significances to perceive circRNAs dynamic change [152].…”

Identification of RNA: 5-Methylcytosine Methyltransferases-Related Signature for Predicting Prognosis in Glioma

“…In recent years, with the advent and development of high-throughput sequencing technologies coupled with direct RNA-sequencing technologies, the focus has shifted to the study of epigenetic modifications of RNA (3,4). Based on these sequencing technologies, published data reveals that RNA contains multiple dynamic modifications, among which the most studied are N6-methyladenosine (m 6 A), 5-methylcytosine (m 5 C), N1methyladenosine (m 1 A), N7-methylguanosine(N 7 G), and ribose 2 ′ -O-methylation, as well as pseudouridine (Ψ ) and inosine (I) (5)(6)(7)(8)(9). The dynamic regulation and disorder of these RNA modifications are also significantly related to the occurrence, maintenance and progression of tumors (10,11).…”

“…The dynamic regulation and disorder of these RNA modifications are also significantly related to the occurrence, maintenance and progression of tumors (10,11). Among these RNA modifications, the m 6 A was the first modification to be identified. Another well-studied modification of RNA is m 5 C (12).…”

A Comprehensive Analysis Identified the Key Differentially Expressed Circular Ribonucleic Acids and Methylation-Related Function in Pheochromocytomas and Paragangliomas

“…et al, 2019). Moreover, circRNAs exhibit abnormal expression in numerous cancer types, including liver, stomach, breast, ovarian, and oral cancers; therefore, they have been considered novel biomarkers for tumor screening and are potential therapeutic targets (Hansen et al, 2013;Conn et al, 2015;Meng et al, 2019;Vo et al, 2019).…”