Circular RNAs: diversity of form and function

Abstract

It is now clear that there is a diversity of circular RNAs in biological systems. Circular RNAs can be produced by the direct ligation of 5 ′ and 3 ′ ends of linear RNAs, as intermediates in RNA processing reactions, or by "backsplicing," wherein a downstream 5 ′ splice site (splice donor) is joined to an upstream 3 ′ splice site (splice acceptor). Circular RNAs have unique properties including the potential for rolling circle amplification of RNA, the ability to rearrange the order of genomic information, protection from exonucleases, and constraints on RNA folding. Circular RNAs can function as templates for viroid and viral replication, as intermediates in RNA processing reactions, as regulators of transcription in cis, as snoRNAs, and as miRNA sponges. Herein, we review the breadth of circular RNAs, their biogenesis and metabolism, and their known and anticipated functions.

Circular RNA participates in the carcinogenesis and the malignant behavior of cancer

“…To date, the evidence suggests that circRNAs may regulate transcription and pathways by manipulating microRNAs. 34,35 The resulting microRNA profiles can act as a distinctive cursor in dividing the induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs); the state of pluripotent stem cell subdivision is of great potential in distinguishing cancer cells from differentiated cells in a p53 network status-related manner. 36 Besides, a negative correlation between global circular RNA abundance and proliferation has been confirmed.…”

The emerging role and clinical implication of human exonic circular RNA

“…1 There are 5 general categories of RNA circles, including genomic circular RNA (viroids and hepatitis delta virus), circular intron RNA (circular intronic RNAs and excised introns), circular processing intermediate RNA (rRNA precursors and permuted tRNAs), circular housekeeping noncoding RNA (some snoRNAs and RNase P), and circular spliced-exon RNA. 2 Circular RNA, derived from back-spliced exons anchored by a breakpoint with flanking GU/AG sequence, is essentially exonic circular RNA (circRNA). For nearly 40 years, a systematic and comprehensive understanding of these covalently closed non-colinear RNAs has been lacking because traditional RNA analysis could not provide reliable high-throughput detection methods.…”

High-throughput sequencing reveals circular substrates for an archaeal RNA ligase

“…For a long time, circular RNA molecules (circRNAs) lacking 3 0 or 5 0 termini were considered an unusual form of nucleic acids found in few viroids or viruses using a single-stranded RNA molecule as genetic material, participating in maturation of some tRNA genes, or, alternatively, a result of aberrant RNA splicing (for recent reviews, see [1][2][3] ). However, numerous recent genome-wide experimental and computational studies (RNAseq analyses) tailored toward detection of circRNAs have revealed this class of RNA molecules as abundant in eukarya, including humans.…”