Interactions of circRNAs with methylation: An important aspect of circRNA biogenesis and function (Review)

Abstract

Circular RNA (circRNA) molecules are noncoding RNAs with unique circular covalently closed structures that contribute to gene expression regulation, protein translation and act as microRNA sponges. circRNAs also have important roles in human disease, particularly tumorigenesis and antitumor processes. Methylation is an epigenetic modification that regulates the expression and roles of DNA and coding RNA and their interactions, as well as of noncoding RNA molecules. Previous studies have focused on the effects of methylation modification on circRNA expression, transport, stability, translation and degradation of circRNAs, as well as how circRNA methylation occurs and the influence of circRNAs on methylation modification processes. circRNA and methylation can also regulate disease pathogenesis via these interactions. In the present study, we define the relationship between circRNAs and methylation, as well as the functions and mechanisms of their interactions during disease progression.

Keywords: DNA; RNA; carcinoma; circular RNA; disease; methylation.

Figure 1.

Effects of methylation on circRNA biogenesis, transport, stability, translation and degradation. (A) METTL3 or YTHDC1 affect circRNA generation by regulating m6A modification. (B) m6A modification regulates circNSUN2 export to the cytoplasm. (C) m6A modification improves circRNA-SORE stability. (D) YTHDF3 and eIF4G2 physically interact with endogenous circ-ZNF609 and can affect circ-ZNF609 translation levels. (E) m6A modification is involved in circRNA degradation via the YTHDF2/HRSP12/RNase P/MRP complex signaling pathway. Gray arrows represent downregulation. circRNA, circular RNA; METTL3, methyltransferase-like 3; YTHDC, YTH domain containing; m6A, N6-methyladenosine; NSUN2, NOP2/Sun RNA methyltransferase 2; YTHDF, YTH domain-containing family protein; eIF4G2, eukaryotic translation initiation factor 4-γ2; ZNF609, zinc finger protein 609; HRSP12, heat-responsive protein 12; MRP, mitochondrial RNA processing enzyme; miRNA, microRNA; FTO, fat mass and obesity-associated protein.