Circular RNAs in Cardiovascular Disease: An Overview

Figure 1

Models of circRNA biogenesis: (a) lariat-driven circularization: exon skipping leads to a covalent splice of the splice donor in 3′ end of exon 1 to the splice acceptor in 5′ end of exon 4, which forms a linear product and a lariat structure containing the skipped exons 2 and 3. Then the lariat is joined by spliceosome and the introns are removed to form a circRNA. (b) Intron-pairing-driven circularization: intron 1 and intron 3, which contain complementary sequence motifs, lead to close proximity through direct base-pairing and form a linear RNA and a circular structure. The splicing of the two introns produces a circRNA (exon-only circRNA), while the generation of an EIciRNA (intron-retaining circRNA) is caused by the presence of a retained intron. (c) Circular intronic RNAs: the existence of 7 nt GU-rich element near exon 1 (yellow box) and 11 nt C-rich element near exon 2 (orange box) makes it possible for an intron to escape debranching when the intron lariat is produced from the splicing reaction. (d) RNA binding proteins (RBPs) driven circularization: the interaction between RBPs (Y-shape) can bind to sequence motifs and bring two flanking introns close together. Then the introns are removed to form a circRNA.

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