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. 2021 Sep 27;9:716462. doi: 10.3389/fcell.2021.716462

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Copyright © 2021 Balandeh, Mohammadshafie, Mahmoudi, Hossein Pourhanifeh, Rajabi, Bahabadi, Mohammadi, Rahimian, Hamblin and Mirzaei.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Circular RNA biogenesis mechanisms. (A) Lariat-driven circularization or exon skipping model. The splice donor at the 3′ end of Exon 1 is covalently attached to the splice acceptor at the 5′ end of Exon 4 creating a lariat via exon skipping. Then, the spliceosome removes the introns for creating a circular RNA. (B) Intron pairing-driven circularization or direct-back splicing model. The successive introns form a circular structure by base pairing, and then are eliminated for forming an exonic circRNA or re-attached to form an EIcircRNA.