Figure 1.

The biogenesis of circRNA

(A) In lariat-driven circularization, the pre-mRNA is partially folded during transcription, and the 5′ donor site of the upstream intron comes close to and attacks the 3′ acceptor site of the downstream intron. A linear mRNA and an exon-containing lariat with a 2′–5′ phosphodiester bond are then formed. After a second splicing reaction, the lariat intermediate is finally transformed into a circular RNA. The final products can be divided into three categories: ecRNA, ciRNA, and EIciRNA. (B) In intron-pairing-driven circularization, complementary flanking intronic sequencing of pre-mRNA leads to the formation of secondary structure, which allows the 5′ end of the downstream intron to attack the 3′ end of the upstream intron to form a circular RNA and a terminated fork product. (C) RNA-binding proteins could promote splicing and circRNA formation by binding flanking introns to make the donor site and the acceptor site closer.