FIGURE 1.

The biogenesis mechanisms and biological roles of circular RNAs. (A) Lariat-driven circularization. (B) Intron pairing–driven circularization. (C) RBP-mediated circularization. (D) Repetitive MIR-mediated circularization. (E) EML4-ALK fusion gene–mediated circularization. (F) SLC34A2-ROS1 fusion gene–mediated circularization. (G) Interfering with gene-mediated circularization that regulates transcription. (a) CircRNAs can sponge miRNAs. (b) A few circRNAs containing the m⁶A motif or IRES can encode functional proteins. (c) CircRNAs splice with linear RNA to promote the expression of mRNA. (d) EIciRNA can interact with U1 small nuclear ribonucleoproteins and then increase the transcription of their host genes by binding with RNA pol II; ciRNA, and the RNA pol II complex can directly interact and play a role in regulating parental gene transcription. (e) CircRNAs can be translated into peptides or proteins. (f) CircRNA in some nuclei is involved in histone modification. (g) Mitochondrial-derived circRNA can regulate the entry of proteins into mitochondria under the interaction of TOM40 and PNPASE. CiRNA, Circular intronic RNA; EcircRNA, Exonic circRNA; EIciRNA, Exon–intron circRNA; RBP, RNA-binding protein; RNA pol II, RNA polymerase II.