Figure 1.

Putative pathways for circRNA biogenesis. A constitutive linear RNA splicing pattern is shown for comparison purposes (A). CircRNA formation may proceed through a direct backsplicing pathway in which circularization can be driven by intron pairing (B, left upper panel) or RNA-binding protein pairing (B, right upper panel) that brings the appropriate splice signals within proximity of each other. A linear RNA containing the skipped exons may be formed as shown in the gray box or may be degraded depending on the kinetics of splicing vs. debranching and exonuclease mediated degradation. Alternatively, circRNAs may be produced through a lariat driven pathway (C) where exon skipping removes the exons to be backspliced from the primary transcript and promotes circularization because the splice signals of the circRNA exon to be are juxtaposed in the lariat structure. The circRNA may be formed concurrently with the linear RNA as shown in the gray box or may not be formed depending on the kinetics of intra-lariat splicing vs. debranching and exonuclease mediated degradation. In all instances, the intronic lariat products are likely rapidly degraded (gray, hatched boxes).