The Functional Roles and Regulation of Circular RNAs during Cellular Stresses

Abstract

Circular RNAs (circRNAs) are a novel class of regulatory RNA involved in many biological, physiological and pathological processes by functioning as a molecular sponge, transcriptional/epigenetic/splicing regulator, modulator of protein–protein interactions, and a template for encoding proteins. Cells are constantly dealing with stimuli from the microenvironment, and proper responses rely on both the precise control of gene expression networks and protein–protein interactions at the molecular level. The critical roles of circRNAs in the regulation of these processes have been heavily studied in the past decades. However, how the microenvironmental stimulation controls the circRNA biogenesis, cellular shuttling, translation efficiency and degradation globally and/or individually remains largely uncharacterized. In this review, how the impact of major microenvironmental stresses on the known transcription factors, splicing modulators and epitranscriptomic regulators, and thereby how they may contribute to the regulation of circRNAs, is discussed. These lines of evidence will provide new insight into how the biogenesis and functions of circRNA can be precisely controlled and targeted for treating human diseases.

Circular RNAs in and out of Cells: Therapeutic Usages of Circular RNAs

“…Yet, clues as to which factors promote the production of circular RNAs were obtained by analyzing the structural characteristics of the host genes from which highly expressed circular RNAs originated; genes containing long introns between exons and actively transcribed genes were found to frequently generate circular RNAs ( Cocquerelle et al, 1992 ; Kristensen et al, 2018 ). Moreover, although the causality between circular RNA expression levels and cellular stress is unknown, it has been reported that the process of circular RNA biogenesis increases when cells are under stress caused by DNA damage, oxidation, and heat shock ( Lee et al, 2022 ). Accordingly, elucidating the molecular mechanisms that increase circular RNA levels under stress conditions should enhance our understanding of the link between circular RNAs and diseases.…”

Long Noncoding RNAs and Circular RNAs Regulate AKT and Its Effectors to Control Cell Functions of Cancer Cells

“…CircR-NAs are other ncRNAs formed by splicing and sequentially connecting between splice donor and acceptor sites, i.e., backsplicing [15]. CircRNAs may function as protein and RNA scaffolds to bind miRNA and regulate transcription or translation in a miRNA and RNA-binding protein sponge manner [16,17].…”