Figure 1.

Classification and biogenesis of circRNAs. (A) Lariat-guided circularization: an exon skipping event leads to a lariat structure that contains exons 2 and 3, formed by the link between the 3′ end of a donor exon with the 5′ end of the acceptor exon, and a linear product consisting of exons 1 and 4. EcircRNA is formed after removal of introns. (B) Circularization is driven by intron-pairing: the pairing of complementary sequences (Alu elements) leads to a circular product and a linear product. Introns are maintained or removed to form an EIciRNA (exon-intron circRNA) or an ecircRNA, respectively. (C) Circular intronic RNA (ciRNA): the splicing reaction generates the intron lariat. An element rich in GU, near the junction site 5′, and an item rich in C, near the branching point, make it stable enough to escape from debranching. (D) Circularization guided by RNA binding proteins (RBP): the interaction between two RBPs joins two flanking introns to form a circRNA and a linear product. (E) tRNA intronic circRNA (tricRNA) originates from pre-tRNA cleaved by the tRNA splicing endonuclease complex.