Fig. 1

Metabolism of circRNA. Regulation of circRNA biogenesis. RBP can modulate circRNA biogenesis by dimerization, ICS stabilization or ICS impairment. ICS in flanking introns can facilitate exon circularization. Biogenesis of circRNA. a In the lariat model, back-spliced exons are skipped and extruded to form an intronic lariat that undergoes further back-splicing, while the remaining exons directly link with each other and form a mature mRNA. b In the direct model, back-splicing occurs first to form a circRNA, leaving an immature linear RNA containing introns. Localization of circRNA c| Long (> 800 nt) or short circRNAs can be translocated to the cytoplasm with the assistance of UAP56 or URH49, respectively. d CircRNAs can be translocated to the cytoplasm in m6A-dependent manner mediated by YTHDC1. e CircRNAs can be excreted to the extracellular space by exosomes. Degradation of circRNA. f Upon viral infection, RNase L activated by 2′-5′-oligoadenosine(2′-5′A) causes the global degradation of circRNAs, which relieves the suppression of PKR. g M6A-containing circRNAs can be recognized by YTHDF2, which interacts with the RNase P/MRP complex bridged by HRSP12, and then the complex endoribonucleolytically cleaves circRNAs. h UPF1 and G3BP1 can bind to imperfect base-paired regions of circRNAs and induce their degradation