Table 2.

Molecular circularization of circRNAs.

CircRNA Biogenesis	CircRNA Product	Biogenesis Mechanism	Refs.
Intron pairing-driven circularization	EcircRNAs or ElciRNAs	The method by which EcircRNA and EIcircRNA cyclize is known as “direct back splicing” or intron pairing-driven cyclization; pre-mRNA containing ALU repeats is sheared to form EcircRNA following reverse-base complementary pairing. EIciRNAs are produced if introns are kept in between exons.	[19,31]
RBP-induced circularization		RBPs (trans-acting factors) are Quaking, Muscleblind, and Fused-in Sarcoma. Circularization is facilitated by bridging comparable intronic regions. RBP dimerization links the 3′ and 5′ ends of circularized exons.	[32,33]
Lariat-induced circularization driven by spliceosomes		Exon circularization is spliceosome-dependent and is collected at the back-splicing site to help join the 5′-3′ donor–acceptor sites. Within lariat, internal splicing releases EcircRNAs or EIcircRNAs.	[34,35,36,37]
Intron self-cyclization	ciRNA	Intron self-cyclization is brought about by the 7 nucleotides of the G/U-rich sequence located near 1 exon and the 11 nucleotides of the C-rich sequence located near another exon in pre-mRNA. Three distinct kinds of circRNAs are produced: ciRNAs, EIcircRNAs, and EcircRNAs. A closed RNA loop (covalently EcircRNA) is formed when the 3′ end of an exon (5’ss) is joined to the 5′ end of either the same exon (single-exon circRNA) or an upstream exon (multiple-exon circRNA).	[22,38,39,40]

[CircRNA: circular RNA; ciRNA: intronic circRNA; EIcircRNA: exon–intron circular RNA; Ecirc: exonic circular RNA; RBP: RNA-binding protein].