Figure 5.

Generation of circular RNAs via exon skipping or a failure to debranch introns. (A) Circular RNA biogenesis can proceed through an exon-containing lariat. Via an alternative splicing event, exon 2 can first be skipped to generate a linear mRNA consisting of exons 1 and 3 as well as an intron lariat intermediate. The lariat can then be re-spliced to generate a circular RNA comprised of exon 2 along with a double lariat, which is subsequently debranched and degraded. (B) Although most intron lariats are rapidly debranched, some are only trimmed to their branch point. This generates a circular intronic RNA that is covalently joined by a 2′-5′ phosphodiester bond between the 5′ end of the intron and the branch point adenosine.