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. 2016 Dec 16;14(8):1035–1045. doi: 10.1080/15476286.2016.1271524

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Figure 2. — Modulators of circRNA biogenesis. (A) Competitive base-pairing between multiple pairs of inverted repeats can modulate circRNA formation as only base-pairing between IRs across an exon (inter-intronic pairing, up) promotes circRNA formation whereas intra-intronic base-pairing does not (down). The 2 mutually exclusive base-pairing patterns are indicated with arrows in the middle panel. (B) Additionally, when dependent on intron-pairing, the efficiency with which circRNAs are formed may be modulated by the activity of the RNA editing enzyme ADAR 1 that acts as an inhibitor of circRNA formation by mediating the conversion of adenosines (A) to inosines (I) thereby destabilizing the base-pairing that promotes backsplicing. (C) Splicing factors, both tissue specific and general, can affect circRNA expression and may either inhibit or promote the expression of a circRNA. (D) CircRNA formation is affected by the rate of transcription, with a high transcriptional elongation rate being favorable for circRNA expression.