Emergent Roles of Circular RNAs in Metabolism and Metabolic Disorders (original) (raw)
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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.
Circad: a comprehensive manually curated resource of circular RNA associated with diseases
Database
Circular RNAs (circRNAs) are unique transcript isoforms characterized by back splicing of exon ends to form a covalently closed loop or circular conformation. These transcript isoforms are now known to be expressed in a variety of organisms across the kingdoms of life. Recent studies have shown the role of circRNAs in a number of diseases and increasing evidence points to their potential application as biomarkers in these diseases. We have created a comprehensive manually curated database of circular RNAs associated with diseases. This database is available at URL http://clingen.igib.res.in/circad/. The Database lists more than 1300 circRNAs associated with 150 diseases and mapping to 113 International Statistical Classification of Diseases (ICD) codes with evidence of association linked to published literature. The database is unique in many ways. Firstly, it provides ready-to-use primers to work with, in order to use circRNAs as biomarkers or to perform functional studies. It addi...
Circular RNAs in cancer and diabetes
2021
Circular RNAs (circRNAs) are a class of noncoding RNA molecules formed by the back splicing process. Compared to linear mRNA molecules they are more stable. CircRNA acts as miRNA sponges, regulates translation, epigenetic alterations, etc. However, the most significant aspect of circRNAs has been its role in regulating the hallmark of cancer and diabetes mellitus. Several circRNAs are extensively expressed in individuals with cancer and diabetics. Dysregulated expression of various circRNAs plays a crucial part in the development of type 2 diabetes mellitus. In the present review, we present the current understanding of cricRNAs biogenesis, regulatory mechanisms, reviews of recent findings and circRNA as potential biomarker.
CircNet: a database of circular RNAs derived from transcriptome sequencing data
Nucleic Acids Research, 2015
Circular RNAs (circRNAs) represent a new type of regulatory noncoding RNA that only recently has been identified and cataloged. Emerging evidence indicates that circRNAs exert a new layer of posttranscriptional regulation of gene expression. In this study, we utilized transcriptome sequencing datasets to systematically identify the expression of circRNAs (including known and newly identified ones by our pipeline) in 464 RNA-seq samples, and then constructed the CircNet database (http://circnet. mbc.nctu.edu.tw/) that provides the following resources: (i) novel circRNAs, (ii) integrated miRNAtarget networks, (iii) expression profiles of circRNA isoforms, (iv) genomic annotations of circRNA isoforms (e.g. 282 948 exon positions), and (v) sequences of circRNA isoforms. The CircNet database is to our knowledge the first public database that provides tissue-specific circRNA expression profiles and circRNA-miRNA-gene regulatory networks. It not only extends the most up to date catalog of circR-NAs but also provides a thorough expression analysis of both previously reported and novel circRNAs. Furthermore, it generates an integrated regulatory network that illustrates the regulation between cir-cRNAs, miRNAs and genes.
Cellular and Molecular Life Sciences, 2019
Circular RNAs (circRNAs) are members of the non-coding transcriptome; however, some of them are translated into proteins. These transcripts have important roles in both physiological and pathological mechanisms due to their ability to directly influence cellular signaling pathways. Specifically, circRNAs are regulators of transcription, translation, protein interaction, and signal transduction. An increased knowledge within their area is observed over the last few years, concomitant with the development of next-generation sequencing techniques. circRNAs are mostly tissue and disease specific with the ability of specifically changing the biological behavior of cells. The altered expression profile is currently investigated as novel minimally invasive diagnosis/prognosis tool and also therapeutic target in human disease. The diagnosis approach is based on their level modification within pathological states, especially cancer, where circRNAs' therapies are intensively explored in anti-aging strategies, diabetes, cardiovascular diseases, and malignant pathologies, and are relying on the restoration of homeostatic profiles.
Circular RNA mediated gene regulation in chronic diabetic complications
Scientific Reports, 2021
Chronic diabetic complications affect multiple organs causing widespread organ damage. Although there are some commonalities, the phenotype of such changes show tissue specific variation. Given this, we examined whether differences in circular RNA (circRNA) mediated gene regulatory mechanisms contribute to changes in gene expression at the basal level and in diabetes. CircRNAs are single-stranded RNA with covalently closed loop structures and act as miRNA sponges, factors of RNA splicing, scaffolding for proteins, regulators of transcription, and modulators of the expression of parental genes, among other roles. We examined heart and retinal tissue from Streptozotocin-induced diabetic mice with established diabetes related tissue damage and tissue from non-diabetic controls. A custom array analysis was performed and the data were analysed. Two major circRNA mediated processes were uniquely upregulated in diabetic heart tissue, namely, positive regulation of endothelial cell migratio...
Comprehensive analysis of circRNA expression profiles in humans by RAISE
International journal of oncology, 2017
Circular RNAs (circRNAs) are pervasively expressed circles of non‑coding RNAs. Even though many circRNAs have been reported in humans, their expression patterns and functions remain poorly understood. In this study, we employed a pipeline named RAISE to detect circRNAs in RNA‑seq data. RAISE can fully characterize circRNA structure and abundance. We evaluated inter-individual variations in circRNA expression in humans by applying this pipeline to numerous non‑poly(A)-selected RNA‑seq data. We identified 59,128 circRNA candidates in 61 human liver samples, with almost no overlap in the circRNA of the recruited samples. Approximately 89% of the circRNAs were detected in one or two samples. In comparison, 10% of the linear mRNAs and non‑coding RNAs were detected in each sample. We estimated the variation in other tissues, especially the circRNA high-abundance tissues, in advance. Only 0.5% of the 50,631 brain circRNA candidates were shared among the 30 recruited brain samples, which is...
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...
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...