Biogenesis and Functions of Circular RNAs Come into Focus. Issue 3 (March 2020)

• Record Type: Journal Article
• Authors: Xiao, Mei-Sheng; Ai, Yuxi; Wilusz, Jeremy E.
• Is Part Of: Trends in cell biology. Volume 30:Issue 3(2020)
• Page Start: 226
• Page End: 240
• Publication Date: 2020-03
• Subjects: circRNA -- backsplicing -- pre-mRNA splicing -- innate immunity -- microRNA -- translation; Cytology -- Periodicals; Cytology -- Research -- Periodicals; 571.6
• DOI: 10.1016/j.tcb.2019.12.004
• Languages: English
• ISSNs: 0962-8924

Abstract

Abstract : Many eukaryotic protein-coding genes are able to generate exonic circular RNAs. Most of these covalently linked transcripts are expressed at low levels, but some accumulate to higher levels than their associated linear mRNAs. We highlight several methodologies that have been developed in recent years to identify and characterize these transcripts, and which have revealed an increasingly detailed view of how circular RNAs can be generated and function. It is now clear that modulation of circular RNA levels can result in a variety of molecular and physiological phenotypes, including effects on the nervous system, innate immunity, microRNAs, and many disease-relevant pathways. Highlights: Circular RNAs are generated from many eukaryotic protein-coding genes when the pre-mRNA splicing machinery 'backsplices' and joins a downstream 5' splice site to an upstream 3' splice site. Circular RNA biogenesis is often facilitated by base pairing between intronic repeat elements, and the expression of these transcripts is further controlled by the combinatorial action of RNA-binding proteins, the levels of core spliceosome components, and exon-skipping events. Once generated, most circular RNAs are highly stable and accumulate in the cytoplasm after being exported from the nucleus in a length-dependent manner. The biological functions of most circular RNAs remain unknown, but it is becoming increasingly clear that specific circular RNAs may modulate the activity of microRNAs or RNA-binding proteins, be translated to yield protein products, or regulate innate immune responses. Circular RNAs are most abundant in neuronal tissues, accumulate with aging, and have functional roles in human diseases including cancer.