Fig. 2

Biogenesis of circRNAs from intronic circRNAs. a Circular intron RNA (ciRNA). The circle formation requires prior release of exon 2. The 2′-OH group of the 3′-terminus attacks the phosphodiester bond near 5′-splice site of the intron, leading to formation of a circular RNA with 2′,5′-phosphodiester. b. Circular RNA from group I introns. An exogenous guanosine(G) attacks the 5′ terminus of the intron and exon 1 is cleaved due to transesterification. The 3′-hydroxyl of the free exon 1 acts as a nucleophile to attack the 5′-terminus of exon 2, producing a linear intron and the ligated exons. The 2′-hydroxyl group near the 3′ terminus of the linear intron attacks the phosphodiester bond near the 5′ terminus, forming a RNA lasso having a 2′,5′-phosphodiester. Finally, a short 3′ tail is released to form a circRNA from group I introns. c. Circular RNA from group II introns. Splicing the pre-mRNA to form a RNA lasso with a 2′,5′-phosphodiester. Then, a ciRNA is formed by removing the 3′ tail of the RNA lasso