Fig. 1

Biogenesis of CircRNA. Pre-mRNA experience either back-splicing, which produces both a circRNA and an alternatively spliced linear RNA without an exon, or typical splicing, which produces a linear RNA with an exon. CircRNAs can form in one of three ways during biogenesis: EIciRNAs, ecircRNAs, and ciRNAs. The process of direct backsplicing, in which the upstream 3ʹ splice acceptor site is covalently connected to the downstream 5ʹ splice donor site of the exon, leads to looping of the precursor mRNA, often resulting in ecircRNAs. Direct backsplicing is also used by EIcircRNAs, although backsplicing leaves certain intron sequences in the circRNA instead of deleting them. Removal of introns during splicing of pre-mRNA is thought to be the cause of ciRNA formation. TricRNA is a type of circular RNA formed by the splicing process of precursor tRNA