Fig. 4

Biogenesis and functions of circRNAs. (1) CircRNAs are primarily generated by back-splicing of pre-mRNA in the nucleus. Long flanking introns complementary sequences (such as inverted repeat elements Alu pairs) and trans acting RNA binding proteins (RBPs) participate in back-splicing to form the circular structures. CircRNAs can also be produced by lariat-intron intermediate. The cyclization of lariat is driven by GU-rich element at the upstream splicing site and C-rich element near the downstream branching point, or AG-GU motifs at both ends. In addition, circRNAs can be generated during the process of pre-tRNA sequence splicing to maturation. Furthermore, a new class of circRNAs can be formed by the cyclization of two intron-containing fragments (ICFs), with GT-AG splicing signals on both sides. (2) There are five types of circRNAs, including (a) EIcircRNA, (b) EcircRNA, (c) CiRNA, (d) TricRNAs and (e) Intergenic circRNAs. (3) It has been reported that circRNAs possess a variety of regulatory functions, such as (A) protein scaffolding, (B) miRNA sponging, (C) regulation of parental gene, (D) protein sponging, (E) protein translation and (F) protein recruitment