R nba circ1/15/2024 ICS in flanking introns can facilitate exon circularization. RBP can modulate circRNA biogenesis by dimerization, ICS stabilization or ICS impairment. Hopefully, this review will help to reveal intricate circRNA-related issues and to develop circRNA-targeted translational research and clinical applications. Therefore, in this article, we reviewed the important progress in the metabolism and functions of circRNAs and highlighted the modes of circRNA-protein interactions. However, studies on circRNA-protein interaction are still lacking, and its mechanisms fascinate scientists. CircRNA-protein interactions have remarkably rejuvenated the field of circRNAs and enlightened our insights into their biological significance. Actually, one circRNA can simultaneously function as both a miR sponge and a protein template (or interactor ).Īdditionally, proteins are direct effectors of almost all vital activities. This inspires us that circRNAs can be versatile and previously-studied circRNAs may also possess other abilities. Another one found that CDR1as interacts with p53 and blocks it from MDM2. Interestingly, a recent study reported that CDR1as interacts with IGF2BP3 and compromises its pro-metastatic functions. Antisense transcript of cerebellar degeneration-related protein 1 (CDR1as) represents the earliest functionally studied circRNAs and expands the competing endogenous RNA (ceRNA) crosstalk network. Moreover, the majority of functional studies have shown that circRNAs act as miR sponges, which are monotonous and stereotypical. However, the mechanisms underlying the abnormal landscape of circRNAs and how circRNAs exert physiological or pathological roles in diseases remain poorly understood. Plenty of studies have uncovered their distinct expression signatures and crucial biological roles in a variety of diseases, such as cancer, cardiovascular disease, neurological disorder and autoimmune disease. The unique structure of circRNAs provides them with a longer half-life and more resistance to RNase R than linear RNAs, which makes them potential candidates for diagnostic biomarkers and therapeutic targets. More recently, an increasing number of investigations have identified multiple functions of circRNAs, including serving as protein scaffolds or miR sponges and being translated into polypeptides. With the development of high-throughput RNA-sequencing and bioinformatic tools, scientists have found that circRNA is a general feature of the human transcriptome and is ubiquitous in many other metazoans. Later, more studies found or synthesized circular forms of RNAs in various species, including viruses, prokaryotes, unicellular eukaryotes and mammals. Single-stranded, covalently closed circRNAs were first reported as viroids, which are pathogens of certain plants, in 1976 and were first detected in human HeLa cells by electron microscopy in 1979. ![]() ![]() This review systematically evaluates the roles and mechanisms of circRNAs, with the hope of advancing translational medicine involving circRNAs. Many discoveries have revealed that circRNAs have unique expression signatures and play crucial roles in a variety of diseases, enabling them to potentially act as diagnostic biomarkers and therapeutic targets. Hence, in this review, we briefly summarize recent progress in the metabolism and functions of circRNAs and elaborately discuss the patterns of circRNA-protein interactions, including altering interactions between proteins, tethering or sequestering proteins, recruiting proteins to chromatin, forming circRNA-protein-mRNA ternary complexes and translocating or redistributing proteins. ![]() However, the existing research on circRNA-protein interactions is quite limited. Moreover, emerging evidence has revealed that a group of circRNAs can serve as protein decoys, scaffolds and recruiters. CircRNAs exert biological functions by acting as transcriptional regulators, microRNA (miR) sponges and protein templates. Important advances have been made in the biogenesis, regulation, localization, degradation and modification of circRNAs. Circular RNAs (CircRNAs) are single-stranded, covalently closed RNA molecules that are ubiquitous across species ranging from viruses to mammals.
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