Figure 1.

Biogenesis of circular RNAs. (A) During transcription, linear and back-splicing of exons rival each other. Back-splicing is facilitated by long flanking introns, cis-elements i.e., intronic complementary elements (ICS), and trans-factors i.e., RNA-binding proteins (RBPs). To facilitate back-splicing, a downstream splice-donor (SD) site is brought in close vicinity with an upstream splice-acceptor (SA) site via base-pairing interactions between ICS or dimerization of RBPs. An upstream branch point (BP) nucleophilically attacks a downstream SD site, which thereafter nucleophilically attacks an upstream SA site, resulting in the creation of exonic circRNAs or exon-intron circRNAs. (B) Alternative splicing events like exon-skipping often generate skipped exon bearing lariat precursors, which can participate in the genesis of exonic circRNAs. (C) Intronic lariat precursors generated by linear canonical splicing can escape lariat debranching and serve as a source for intronic circRNAs.