Fig. 3

Regulation of circRNA biogenesis by RBPs. The majority of circRNAs originate form exons with ICSs or specific binding motifs in their flanking introns. Certain RBPs, such as ESRP1, recognizes its binding motifs to facilitate circularization of exons independent of other ICSs, such as Alu elements. Others, such as QKI and EIF4A3, on the other hand, attach to and stabilize formed ICS pairs. On the contrary, RNA helicase, such as ADAR1, unwinds ICS pairs to inhibit back-splicing and promotes linear splicing of pre-mRNAs. ADAR1, adenosine deaminases acting on RNA 1; circRNA, circular RNA; EIF4A3, Eukaryotic translation initiation factor 4A3; ICS, inverted complementary sequence; mRNA, messenger RNA; QKI, quaking