Emerging roles and context of circular RNAs

Abstract

Circular RNAs (CircRNAs) represent a large class of noncoding RNAs (ncRNAs) that have recently emerged as regulators of gene expression. They have been shown to suppress microRNAs, thereby increasing the translation and stability of targets of such microRNAs. In this review, we discuss the emerging functions of circRNAs, including RNA transcription, splicing, turnover, and translation. We also discuss other possible facets of circRNAs that can influence their function depending on the cell context, such as circRNA abundance, subcellular localization, interacting partners (RNA, DNA, and proteins), dynamic changes in interactions following stimulation, and potential circRNA translation. The ensuing changes in gene expression patterns elicited by circRNAs are proposed to drive key cellular processes, such as cell proliferation, differentiation and survival, that govern health and disease.

Extracellular RNA profiles with human age

“…Here, we have used a combination approach and identified 133 extracellular circRNAs (ex‐circRNAs) and further validated age‐related changes in three different ex‐circRNAs: circ_1305 , circ_722, and circ_1445 . Emerging data suggest that circRNAs can function to sponge miRNAs and RBPs (Panda, Grammatikakis, Munk, Gorospe & Abdelmohsen, 2017). Here, we have identified several serum miRNAs that are predicted to bind to the ex‐circRNAs and also with several RBPs.…”

miR-192 Is Overexpressed and Promotes Cell Proliferation in Prostate Cancer

“…For example, Karreth et al [5] reported that miR-653, miR-134, and miR543 mediated the effect of BRAFP1 on BRAF expression and MAPK activation. Li et al [6] also found that miR-7, miR-17, and miR-214 could mediate the regulation of circ-ITCH in inhibiting esophageal squamous cell carcinoma development by suppressing the Wnt/β-catenin pathway. Therefore, exploring the functions of miRNAs could provide novel insights to identify the mechanisms underlying disease progression.…”

Profiles and Bioinformatics Analysis of Differentially Expressed Circrnas in Taxol-Resistant Non-Small Cell Lung Cancer Cells

“…Intronic circRNAs consist of lariat introns. Exonintron circRNAs contain both exons and introns [16,18]. Mounting evidence indicates that circRNAs could be free from RNase R digestion to protect the special circular construction and thus are more stable than linear mRNAs, possibly explaining their long half-lives [19,20].…”

“…The formation of circRNAs hiding translation start sites could impede the translation of residual linear transcripts, referred to as the "mRNA trap," indicating the competition of circRNAs with pre-mRNAs of their host genes [15,25]. Additionally, circRNAs exert regulatory effects by binding to lncRNAs, transcription factors, and RNA-binding proteins, which, at the same time, results in feedback behavior on circRNA stability, abundance, and/or localization [16,26]. In aggregate, the mechanisms by which circRNAs modulate gene expression are intricate and variable.…”

“…Initially, circRNAs were mistakenly interpreted as a fraction of splicing errors or functionless transcriptional byproducts during pre-mRNA splicing [14]. However, advances in high-throughput sequencing technologies and bioinformatics methods have shed light on their biogenesis, characteristics, and functions, demonstrating the dramatic diversity of RNAs and the complexity of eukaryotic transcriptomes [15,16]. Unlike linear RNAs with 5′ and 3′ termini, circRNAs possess a covalently closed loop structure generated from exon and/or intron circularization, which leads to the deletion of 5′-3′ polarity and the polyadenylated tail [17].…”