Fig. 3

Abundant circRNAs are highly conserved and enriched with Alu repeats, synonymous constraint elements (SCEs), and putative miRNA binding sites. a Genomic location of circHIPK3 illustrates genomic annotations, incl. miRNA target sites (black bars), SCEs (purple), evolutionary conservation level (blue), and Alu repeat elements in inverted directions (black). b Density plots of the distance between the closest pair of inverted homologous Alu repeats surrounding abundant circRNAs, non-abundant circRNAs, and linearly spliced exons, omitting the size of the circRNAs or spliced exons themselves. c Density plots of the average PhyloP position-specific conservation score of the four core nucleotides involved in splicing. d, e The fraction of linearly spliced exons, non-abundant circularized coding exons, and abundant circularized coding exons that contain d SCEs and e conserved miRNA binding regions. *P < 0.5, ***P < 0.001 (χ ² test). f Expected versus observed SCE length of overlap for abundant circRNAs composed of coding exons (n = 243). g Expected versus observed number of miRNA target sites for abundant circRNAs (exonic circRNAs and all non-exonic circRNAs shorter than 10,000 bp were included; n = 270). h The maximal number of binding sites for individual miRNAs within each circRNA (exonic circRNAs and all non-exonic circRNAs shorter than 10,000 bp were included, n = 270). The miRNA with most binding sites are noted for the two top-ranked circRNAs