The emerging landscape of circular RNA in life processes

Figures & data

Figure 1. Schematic presentation of circRNA classification. (A) Sense or exonic, when overlapping one or more exons of the linear transcript on the same strand. (B) Intronic, when arising from an intron of the linear transcript in either sense or antisense orientation. (C) Antisense, when overlapping one or more exons of the linear transcript, as they transcribe from the opposite strand. (D) Bidirectional or intragenic, when transcribing from same gene locus of the linear transcript, but in close genomic proximity within 1 kb and not classified into ‘sense’ and ‘intronic’. (E) Intergenic, when it locates outside at least 1kb away from known gene locus.

Figure 2. Biological functions of circular RNAs. CircRNAs contain miRNA binding sites to act as competitive endogenous RNA. CircRNAs sequester miRNAs from binding mRNA targets. EIciRNAs can enhance gene transcription via interacting with U1 snRNP and RNA Polymerase II in the promoter region of the host gene. GU-rich sequences near the 5’ splice site (red box) and C-rich sequences near branch point (purple box) are minimally sufficient for ciRNA formation. The stable ciRNA binds to elongating RNA Pol II and promotes transcription. CircRNA biogenesis competes with linear splicing. Circularization and splicing compete against each other to keep the transcripts dynamic balance. CircRNA formation act as ‘mRNA trap’ to make linear transcripts untranslated by sequestering the translation start site or break the integrity of mature linear RNA. CircRNAs can also function as RNA binding protein (RBP) sponge to interact with RBPs, such as MBL, p21 and CDK2.

Table 1. circRNAs in the life processes.

Circular RNA	Biological process	References
CDR1as/ciRS-7	Regulate the development of midbrain via acting as miR-7 sponge in zebrafish embryos	^18
	Promote insulin biosynthesis and secretion through CDR1as/miR-7 pathway in islet cells	^34
circRNA cZNF292	Control proliferation and angiogenic sprouting of endothelial cells	^58
hsa_circ_0023404/ circRNA-CER	Participate in the process of chondrocyte extracellular matrix degradation	^64
cANRIL	Regulate INK4/ARF transcription and atherosclerotic vascular disease risk	^38
mm9-circ-012559/ circRNA HRCR	Protect the heart from pathological hypertrophy and heart failure via targeting miR-223 in mice	^27
circ-ITCH	Inhibit cell proliferation and tumor growth via acting as a sponge of miR-7, miR-17 and miR-124 in esophageal squamous cell carcinoma	^25
	Inhibit cell proliferation via interacting with miR-7, miR-20a and miR-214 in colorectal cancer	^43
circ-Foxo3	Suppress tumor growth, cancer cell proliferation and survival in breast cancer (MDA-MB-231 cell)	^26
	Block cell cycle progression by forming a ternary complex with CDK2 and p21	^31
	Promote cardiac senescence by modulating ID-1, E2F1, FAK, and HIF1α in mice	^57
circHIPK3	Inhibit human cell growth by sponging multiple miRNAs	^53
hsa_circ_001569	Promote the proliferation and invasion of colorectal cancer cells	^54
F-circM9	Contribute to leukemia progression and confer resistance to treatment in leukemic cells	^70