Theranostics 2020; 10(8):3503-3517. doi:10.7150/thno.42174


Circular RNA-protein interactions: functions, mechanisms, and identification

Anqing Huang1, Haoxiao Zheng1, Zhiye Wu2, Minsheng Chen2,✉, Yuli Huang1,3,✉

1. Department of Cardiology, Shunde Hospital, Southern Medical University, Jiazhi Road, Lunjiao Town, Shunde District, Foshan, 528300, China.
2. Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
3. The George Institute for Global Health, NSW 2042 Australia.

This is an open access article distributed under the terms of the Creative Commons Attribution License ( See for full terms and conditions.
Huang A, Zheng H, Wu Z, Chen M, Huang Y. Circular RNA-protein interactions: functions, mechanisms, and identification. Theranostics 2020; 10(8):3503-3517. doi:10.7150/thno.42174. Available from

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Circular RNAs (circRNAs) are covalently closed, endogenous RNAs with no 5′ end caps or 3′ poly(A) tails. These RNAs are expressed in tissue-specific, cell-specific, and developmental stage-specific patterns. The biogenesis of circRNAs is now known to be regulated by multiple specific factors; however, circRNAs were previously thought to be insignificant byproducts of splicing errors. Recent studies have demonstrated their activity as microRNA (miRNA) sponges as well as protein sponges, decoys, scaffolds, and recruiters, and some circRNAs even act as translation templates in multiple pathophysiological processes. CircRNAs bind and sequester specific proteins to appropriate subcellular positions, and they participate in modulating certain protein-protein and protein-RNA interactions. Conversely, several proteins play an indispensable role in the life cycle of circRNAs from biogenesis to degradation. However, the exact mechanisms of these interactions between proteins and circRNAs remain unknown. Here, we review the current knowledge regarding circRNA-protein interactions and the methods used to identify and characterize these interactions. We also summarize new insights into the potential mechanisms underlying these interactions.

Keywords: circular RNAs (circRNAs), RNA binding proteins (RBPs), biogenesis, degradation, translation