Figure 1.

In typical canonical splicing (up), introns are excluded from immature pre-messenger RNA with covalent bonds forming between exons, the mature messenger RNA is completed with a 5′ cap and 3′ polyA tail; In circRNA biogenesis (down), a “back-splice” junction is formed between the 5′ splice donor site and an upstream 3′ acceptor site to form a circular molecule. Typical pathways include (a) reverse complementary nucleotide sequences in flanking introns, typically long Alu repeats, (b) RNA binding protein-mediated, and through lariat precursors, which may be a result of (c) exon skipping and (d) introns evading degradation; A variety of mature circRNA molecules can form from a single pre-messenger RNA sequence, including (i) multi-exonic, (ii) single exonic, (iii) exon-intronic, and (iv) intronic isoforms; Proposed endogenous functions are highlighted.