Fig. 1

Biosynthesis of ecircRNA and EIciRNA. a Exon-skipping or lariat-driven circularisation. First, a pre-mRNA is spliced, causing the 3′-hydroxyl of the upstream exon to covalently bond to the 5′-phosphate of the downstream exon. At the same time, the sequence between the exons becomes an RNA lariat containing several exons and introns. Second, in the RNA lariat, the 2′-hydroxyl of the 5′-intron reacts with the 5′-phosphate of the 3′-intron, followed by the 3′-hydroxyl of the 3′-exon reacting with the 5′-phosphate of the 5′-exon. As a result, an RNA double lariat and a circular RNA are produced. Finally, some introns of the circular RNA are removed, producing an ecircRNA or EIcirRNA. b. Direct back-splicing or intron-pairing-driven circularisation. First, the upstream intron pairs with the downstream intron. Second, the 2′-hydroxyl of the upstream intron reacts with the 5′-phosphate of the downstream intron, followed by the 3′-hydroxyl of the 3′-exon reacting with the 5′-phosphate of the 5′-exon. Thus, a circular RNA is produced. Finally, some introns of the circular RNA are removed, producing an ecircRNA or EIcirRNA. c. RNA-binding-protein-driven circularisation. First, RNA binding proteins (RBPs) bind the upstream and downstream introns. Second, the RBPs are attracted to each other, and form a bridge between the introns. Third, the 2′-hydroxyl of the upstream intron reacts with the 5′-phosphate of the downstream intron, followed by the 3′-hydroxyl of the 3′-exon reacting with the 5′-phosphate of the 5′-exon. Thus, a circular RNA is produced. Finally, some introns of the circular RNA are removed, producing an ecircRNA or EIcirRNA