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Crit Rev Biochem Mol Biol. 2017 Apr;52(2):220-233. doi: 10.1080/10409238.2016.1276882. Epub 2017 Jan 17.

CircRNAs: a regulator of cellular stress.

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a McKusick-Nathans Institute of Genetic Medicine, School of Medicine , Johns Hopkins University , Baltimore , MD , USA.
b Department of Biochemistry and Molecular Biology , Bloomberg School of Public Health, Johns Hopkins University , Baltimore , MD , USA.
c Department of Oncology , School of Medicine, Johns Hopkins University , Baltimore , MD , USA.


Circular RNAs (CircRNAs) were first identified as a viroid and later found to also be an endogenous RNA splicing product in eukaryotes. In recent years, a series of RNA-sequencing analyses from a diverse range of eukaryotes have shed new light on these eukaryotic circRNAs, revealing dynamic expression patterns in various developmental stages and physiological conditions. In this review, we focus on circRNAs implicated in stress response pathways and explore potential mechanisms underlying their regulation. To date, circRNAs have been shown to act as scaffolds in the assembly of protein complexes, sequester proteins from native subcellular localization, activate transcription of parental genes, inhibit RNA-protein interactions, and function as regulators of microRNA activity. Although the mechanism modulating circRNA levels during stress remains unclear, circRNAs are shown to be regulated during biogenesis, degradation, and exportation. As circRNAs do not have 5' and 3' ends, there are no entry points for exoribonucleases to initiate degradation. Such inherent stability makes this class of RNA a strong candidate to maintain homeostasis in the face of environmental challenges.


Circular RNA; RNA stability; back-splicing; circRNA biogenesis; circRNA degradation; circularization; environment; stress

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