Circular RNAs (original) (raw)

The biogenesis, biology and characterization of circular RNAs

Nature Reviews Genetics, 2019

| Circular RNAs (circRNAs) are covalently closed, endogenous biomolecules in eukaryotes with tissue-specific and cell-specific expression patterns, whose biogenesis is regulated by specific cis-acting elements and transacting factors. Some circRNAs are abundant and evolutionarily conserved, and many circRNAs exert important biological functions by acting as microRNA or protein inhibitors ('sponges'), by regulating protein function or by being translated themselves. Furthermore, circRNAs have been implicated in diseases such as diabetes mellitus, neurological disorders, cardiovascular diseases and cancer. Although the circular nature of these transcripts makes their detection, quantification and functional characterization challenging, recent advances in high-throughput RNA sequencing and circRNA-specific computational tools have driven the development of state-of-the-art approaches for their identification, and novel approaches to functional characterization are emerging.

Circular RNAs: analysis, expression and potential functions

Development (Cambridge, England), 2016

Just a few years ago, it had been assumed that the dominant RNA isoforms produced from eukaryotic genes were variants of messenger RNA, functioning as intermediates in gene expression. In early 2012, however, a surprising discovery was made: circular RNA (circRNA) was shown to be a transcriptional product in thousands of human and mouse genes and in hundreds of cases constituted the dominant RNA isoform. Subsequent studies revealed that the expression of circRNAs is developmentally regulated, tissue and cell-type specific, and shared across the eukaryotic tree of life. These features suggest important functions for these molecules. Here, we describe major advances in the field of circRNA biology, focusing on the regulation of and functional roles played by these molecules.

Deep Insights in Circular RNAs: from biogenesis to therapeutics

Biological Procedures Online, 2020

Circular RNAs (circRNAs) have emerged as a universal novel class of eukaryotic non-coding RNA (ncRNA) molecules and are becoming a new research hotspot in RNA biology. They form a covalent loop without 5′ cap and 3′ tail, unlike their linear counterparts. Endogenous circRNAs in mammalian cells are abundantly conserved and discovered so far. In the biogenesis of circRNAs exonic, intronic, reverse complementary sequences or RNA-binding proteins (RBPs) play a very important role. Interestingly, the majority of them are highly conserved, stable, resistant to RNase R and show developmental-stage/tissue-specific expression. CircRNAs play multifunctional roles as microRNA (miRNA) sponges, regulators of transcription and post-transcription, parental gene expression and translation of proteins in various diseased conditions. Growing evidence shows that circRNAs play an important role in neurological disorders, atherosclerotic vascular disease, and cancer and potentially serve as diagnostic o...

Insights into circular RNA biology

RNA biology, 2016

Circular RNAs (circRNAs) are a novel class of non-coding RNA characterized by a covalently closed-loop structure generated through a special type of alternative splicing termed backsplicing. CircRNAs are emerging as a heterogeneous class of molecules involved in modulating gene expression by regulation of transcription, protein and miRNA functions. CircRNA expression is cell type and tissue specific and can be largely independent of the expression level of the linear host gene, indicating that regulation of expression might be an important aspect with regard to control of circRNA function. In this review, a brief introduction to the characteristics that define a circRNA will be given followed by a discussion of putative biogenesis pathways and modulators of circRNA expression as well as of the stage at which circRNA formation takes place. A brief summary of circRNA functions will also be provided and lastly, an outlook with a focus on unanswered questions regarding circRNA biology w...

Circular RNAs and Its Biological Functions in Health and Disease

Gene Expression and Phenotypic Traits [Working Title], 2019

Circular RNAs (circRNAs) belong to the family of long noncoding RNAs (lncRNA) that, unlike linear RNAs, are characterized by a covalently closed circular RNA structure lacking 5 0 cap and 3 0 poly-adenylated tails. circRNAs have a role in epigenetic regulation of downstream targets. circRNAs play a crucial role in regulating gene and protein expressions by acting as a microRNA (miRNA) sponge and RNA binding protein (RBP) sponge and interact with proteins to affect cell behavior. circRNA expression profiles differ between physiological and pathological states. Moreover, the expression patterns of circRNAs exhibit differences in a tissue-specific manner. Although investigations on circRNAs have been exploding nowadays, yet only a limited number of circRNAs are identified. Furthermore, further researches are needed to shed light on their functions and targets. Therefore, circRNAs are becoming vital as potential biomarkers that may be used for the diagnosis and treatment of diseases. In this chapter, we review the current advancement of cirRNAs with regard to their biogenesis, biological functions, gene regulatory mechanisms, and implications in human diseases and summarize the recent studies on circRNAs as potential diagnostic and prognostic biomarkers based on existing knowledge.

Circular RNAs: Identification, biogenesis and function

Biochimica et biophysica acta, 2015

Circular RNAs are a novel class of non-coding RNA characterized by the presence of a covalent bond linking the 3' and 5' ends generated by backsplicing. Circular RNAs are widely expressed in a tissue and developmental-stage specific pattern and a subset displays conservation across species. Functional circRNAs have been shown to act as cytoplasmic microRNA sponges and RNA-binding protein sequestering agents as well as nuclear transcriptional regulators, illustrating the relevance of circular RNAs as participants in the regulatory networks governing gene expression. Here, we review the features that characterize circular RNAs, discuss putative circular RNA biogenesis pathways as well as review the uncovered functions of circular RNAs.

Circular RNA – New member of noncoding RNA with novel functions Impact statement

The accumulating evidence indicate that circular RNA (circRNA) is a novel class of noncoding RNA with diverse molecular functions. Our review summarizes the current hypotheses for the models of circRNA biosynthesis including the direct interaction between upstream and downstream introns and lariat-driven circular-ization. In addition, molecular functions such as a decoy of microRNA (miRNA) termed miRNA sponge, transcriptional regulator, and protein-like modulator are also discussed. Finally, we reviewed the potential roles of circRNAs in neural system, cardiovascular system as well as cancers. These should provide insightful information for studying the regulation and functions of circRNA in other model of human diseases. Abstract A growing body of evidence indicates that circular RNAs are not simply a side product of splicing but a new class of noncoding RNAs in higher eukaryotes. The progression for the studies of circular RNAs is accelerated by combination of several advanced technologies such as next generation sequencing, gene silencing (small interfering RNAs) and editing (CRISPR/Cas9). More and more studies showed that dysregulated expression of circular RNAs plays critical roles during the development of several human diseases. Herein, we review the current advance of circular RNAs for their biosynthesis, molecular functions, and implications in human diseases.

Circular RNAs: New Players in Gene Regulation

The existence of circular RNAs (circRNAs) was demonstrated over 30 years ago. They did not gain much interest at the time because they appeared to be relatively rare when compared to the abundance of the canonical linear RNAs. However, more recent evidence suggests that circRNAs are abundant in cells and tissues and possess intriguing biological properties. These recent developments have renewed our interest in this novel class of molecules. This report will provide an overview of circRNAs, discuss how they may modify our understanding of gene regulation and indicate their most likely relevance to health. The circRNAs from viruses, bacteria and archaea are not in the scope of this report, and we focused this review on circRNAs in eukaryotes.

Circular RNAs: Biogenesis, Function and Role in Human Diseases

Frontiers in molecular biosciences, 2017

Circular RNAs (circRNAs) are currently classed as non-coding RNA (ncRNA) that, unlike linear RNAs, form covalently closed continuous loops and act as gene regulators in mammals. They were originally thought to represent errors in splicing and considered to be of low abundance, however, there is now an increased appreciation of their important function in gene regulation. circRNAs are differentially generated by backsplicing of exons or from lariat introns. Unlike linear RNA, the 3' and 5' ends normally present in an RNA molecule have been joined together by covalent bonds leading to circularization. Interestingly, they have been found to be abundant, evolutionally conserved and relatively stable in the cytoplasm. These features confer numerous potential functions to circRNAs, such as acting as miRNA sponges, or binding to RNA-associated proteins to form RNA-protein complexes that regulate gene transcription. It has been proposed that circRNA regulate gene expression at the t...