Mechanisms of circular RNA degradation

Abstract

Circular RNAs (CircRNAs) are a class of noncoding RNAs formed by backsplicing during cotranscriptional and posttranscriptional processes, and they widely exist in various organisms. CircRNAs have multiple biological functions and are associated with the occurrence and development of many diseases. While the biogenesis and biological function of circRNAs have been extensively studied, there are few studies on circRNA degradation and only a few pathways for specific circRNA degradation have been identified. Here we outline basic information about circRNAs, summarize the research on the circRNA degradation mechanisms and discusses where this field might head, hoping to provide some inspiration and guidance for scholars who aim to study the degradation of circRNAs.

Circular RNAs and the regulation of gene expression in diabetic nephropathy (Review)

“…The nuclear export of short circRNAs (<400 nt) is regulated by URH49, whereas the export of long circRNAs (>1,200 nt) is controlled by UAP56. The export mechanism for circRNAs with intermediate lengths has not been completely elucidated ( 34 , 35 ).…”

“…Mechanisms for circRNA degradation are mediated by ribonucleases, by the formation of circRNA-protein complexes, by the m6A modification of circRNA or by its packing into exosomes ( 35 ) ( Fig. 1C and D ).…”

“…Certain circRNAs form DNA:RNA hybrids, displacing a single-stranded DNA (R-loops), which are susceptible to degradation by ribonuclease (RNase) H1. On the other hand, after cell inflammation or viral infection, circRNAs can be degraded by activated RNase L ( 35 ) ( Fig. 1C ).…”

“…1C ). Degradation of circRNAs is also mediated by trimethylamine-n-oxide, a byproduct of high sugar and fat diet metabolism of gut microbiota ( 35 ) ( Fig. 1C ).…”

“…Argonaute 2 protein, a member of the Argonaute family, also mediates circRNA degradation by recognizing, cleaving and degrading the circRNA-miRNA complex. Other proteins, such as glycine-trytophan protein of 182 kDa, which has an Ago-binding domain and an RNA-recognition motif among other domains, regulate the degradation of certain circRNAs in an Ago-independent manner ( 35 ). Another two RBPs, namely up-frameshift protein 1 (UPF1) and Ras-GapSH3 domain-binding protein 1 (G3BP1), which exhibit helicase and GTPase activity, respectively, regulate the degradation of circRNAs depending on the highly folded tridimensional structure present in the majority of these molecules ( 35 ) ( Fig.…”