N6-Methyladenosine Modification Opens a New Chapter in Circular RNA Biology

As the most abundant internal modification in eukaryotic cells, N6-methyladenosine (m6A) in mRNA has shown widespread regulatory roles in a variety of physiological processes and disease progressions. Circular RNAs (circRNAs) are a class of covalently closed circular RNA molecules and play an essential role in the pathogenesis of various diseases. Recently, accumulating evidence has shown that m6A modification is widely existed in circRNAs and found its key biological functions in regulating circRNA metabolism, including biogenesis, translation, degradation and cellular localization. Through regulating circRNAs, studies have shown the important roles of m6A modification in circRNAs during immunity and multiple diseases, which represents a new layer of control in physiological processes and disease progressions. In this review, we focused on the roles played by m6A in circRNA metabolism, summarized the regulatory mechanisms of m6A-modified circRNAs in immunity and diseases, and discussed the current challenges to study m6A modification in circRNAs and the possible future directions, providing a comprehensive insight into understanding m6A modification of circRNAs in RNA epigenetics.

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The Landscape Of Circular RNA Expression In The Human Brain

10.1101/500991 ◽

2018 ◽

Cited By ~ 2

Author(s):

Akira Gokoolparsadh ◽

Firoz Anwar ◽

Irina Voineagu

Keyword(s):

Human Brain ◽

Circular Rna ◽

Individual Variability ◽

Mammalian Brain ◽

Circular Rnas ◽

Healthy Individuals ◽

Rna Molecules ◽

Adult Lifespan ◽

Insight Into ◽

Expression Module

ABSTRACTCircular RNAs (circRNAs) are enriched in the mammalian brain and are upregulated in response to neuronal differentiation and depolarisation. These RNA molecules, formed by non-canonical back-splicing, have both regulatory and translational potential. Here, we carried out an extensive characterisation of circRNA expression in the human brain, in nearly two hundred human brain samples, from both healthy individuals and autism cases. We identify hundreds of novel circRNAs and demonstrate that circRNAs are not expressed stochastically, but rather as major isoforms. We characterise inter-individual variability of circRNA expression in the human brain and show that inter-individual variability is less pronounced than variability between cerebral cortex and cerebellum. We also find that circRNA expression is dynamic during cellular maturation in brain organoids, but remains largely stable across the adult lifespan. Finally, we identify a circRNA co-expression module upregulated in autism samples, thereby adding another layer of complexity to the transcriptome changes observed in autism brain. These data provide a comprehensive catalogue of circRNAs as well as a deeper insight into their expression in the human brain, and are available as a free resource in browsable format at: http://www.voineagulab.unsw.edu.au/circ_rna

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Circular RNA MTO1 Inhibits the Proliferation and Invasion of Ovarian Cancer Cells Through the miR-182-5p/KLF15 Axis

Cell Transplantation ◽

10.1177/0963689720943613 ◽

2020 ◽

Vol 29 ◽

pp. 096368972094361 ◽

Cited By ~ 1

Author(s):

Ning Wang ◽

Qin-Xue Cao ◽

Jun Tian ◽

Lu Ren ◽

Hai-Ling Cheng ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Cancer Progression ◽

Circular Rna ◽

Circular Rnas ◽

Ovarian Cancer Cells ◽

Biological Functions ◽

Physiological Processes ◽

Cancer Tissues ◽

Proliferation And Invasion

Circular RNAs (circRNAs) are a novel class of endogenous noncoding RNAs and have been shown to play important roles in a variety of physiological processes. Recently, dysregulation of circRNAs has been identified in many types of cancers. In this study, we analyzed the expression profile and biological functions of circMTO1 in ovarian cancer. We demonstrated that circMTO1 was downregulated in ovarian cancer tissues and cell lines. Upregulation of circMTO1 inhibited proliferation and invasion of ovarian cancer cells while downregulation of circMTO1 promoted these processes. Mechanistically, we showed that circMTO1 sponged miR-182-5p to support KLF15 expression, eventually leading to inhibition of ovarian cancer progression. In conclusion, our study suggested circMTO1 as a novel biomarker and therapeutic target for ovarian cancer treatment.

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Circular RNA: metabolism, functions and interactions with proteins

Molecular Cancer ◽

10.1186/s12943-020-01286-3 ◽

2020 ◽

Vol 19 (1) ◽

Author(s):

Wei-Yi Zhou ◽

Ze-Rong Cai ◽

Jia Liu ◽

De-Shen Wang ◽

Huai-Qiang Ju ◽

...

Keyword(s):

Protein Interactions ◽

Translational Medicine ◽

Transcriptional Regulators ◽

Circular Rna ◽

Ternary Complexes ◽

Circular Rnas ◽

Biological Functions ◽

Diagnostic Biomarkers ◽

Rna Molecules ◽

Made In

AbstractCircular RNAs (CircRNAs) are single-stranded, covalently closed RNA molecules that are ubiquitous across species ranging from viruses to mammals. Important advances have been made in the biogenesis, regulation, localization, degradation and modification of circRNAs. CircRNAs exert biological functions by acting as transcriptional regulators, microRNA (miR) sponges and protein templates. Moreover, emerging evidence has revealed that a group of circRNAs can serve as protein decoys, scaffolds and recruiters. However, the existing research on circRNA-protein interactions is quite limited. 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. 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. This review systematically evaluates the roles and mechanisms of circRNAs, with the hope of advancing translational medicine involving circRNAs.

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The Regulatory Functions of Circular RNAs in Digestive System Cancers

Cancers ◽

10.3390/cancers12030770 ◽

2020 ◽

Vol 12 (3) ◽

pp. 770 ◽

Cited By ~ 4

Author(s):

Xiao Yuan ◽

Ya Yuan ◽

Zhi He ◽

Diyan Li ◽

Bo Zeng ◽

...

Keyword(s):

Digestive System ◽

Rna Binding ◽

Rna Binding Proteins ◽

Circular Rna ◽

Research Progress ◽

Circular Rnas ◽

Biological Functions ◽

Ribonucleic Acids ◽

Mirna Sponges ◽

And Biological Markers

Circular ribonucleic acids (circRNAs), which are a type of covalently closed circular RNA, are receiving increasing attention. An increasing amount of evidence suggests that circRNAs are involved in the biogenesis and development of multiple diseases such as digestive system cancers. Dysregulated circRNAs have been found to act as oncogenes or tumour suppressors in digestive system cancers. Moreover, circRNAs are related to ageing and a wide variety of processes in tumour cells, such as cell apoptosis, invasion, migration, and proliferation. Moreover, circRNAs can perform a remarkable multitude of biological functions, such as regulating splicing or transcription, binding RNA-binding proteins to enable function, acting as microRNA (miRNA) sponges, and undergoing translated into proteins. However, in digestive system cancers, circRNAs function mainly as miRNA sponges. Herein, we summarise the latest research progress on biological functions of circRNAs in digestive system cancers. This review serves as a synopsis of potential therapeutic targets and biological markers for digestive system cancer.

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Circular RNA as a potential diagnostic and/or therapeutic target for endometriosis

Biomarkers in Medicine ◽

10.2217/bmm-2020-0167 ◽

2020 ◽

Vol 14 (13) ◽

pp. 1277-1287

Author(s):

Parisa M Dana ◽

Mona Taghavipour ◽

Hamed Mirzaei ◽

Bahman Yousefi ◽

Bahram Moazzami ◽

...

Keyword(s):

Gene Expression ◽

Signaling Pathways ◽

Therapeutic Target ◽

Noncoding Rnas ◽

Circular Rna ◽

Circular Rnas ◽

Biological Functions ◽

Parental Gene

Endometriosis is a pathology form of endometrium that behaves in a similar way to malignancies, such as invasion and resistance to apoptosis. Circular RNAs (CircRNAs) are a class of noncoding RNAs that have several biological functions including, miRNA sponging, sequestering of proteins, enhancing parental gene expression and translation resulting in polypeptides. In this review, we highlighted the roles of circRNAs as potential diagnostic and therapeutic biomarkers in endometriosis. Moreover, we summarized the roles of circRNAs in the pathogenesis of endometriosis via different signaling pathways, such as the miRNA network and apoptosis.

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The potential of using blood circular RNA as liquid biopsy biomarker for human diseases

Protein & Cell ◽

10.1007/s13238-020-00799-3 ◽

2020 ◽

Author(s):

Guoxia Wen ◽

Tong Zhou ◽

Wanjun Gu

Keyword(s):

Liquid Biopsy ◽

Developmental Stages ◽

Current Knowledge ◽

Cell Types ◽

Circular Rna ◽

Disease Diagnosis ◽

Human Diseases ◽

Biological Functions ◽

Aberrant Expression ◽

Physiological Processes

Abstract Circular RNA (circRNA) is a novel class of single-stranded RNAs with a closed loop structure. The majority of circRNAs are formed by a back-splicing process in pre-mRNA splicing. Their expression is dynamically regulated and shows spatiotemporal patterns among cell types, tissues and developmental stages. CircRNAs have important biological functions in many physiological processes, and their aberrant expression is implicated in many human diseases. Due to their high stability, circRNAs are becoming promising biomarkers in many human diseases, such as cardiovascular diseases, autoimmune diseases and human cancers. In this review, we focus on the translational potential of using human blood circRNAs as liquid biopsy biomarkers for human diseases. We highlight their abundant expression, essential biological functions and significant correlations to human diseases in various components of peripheral blood, including whole blood, blood cells and extracellular vesicles. In addition, we summarize the current knowledge of blood circRNA biomarkers for disease diagnosis or prognosis.

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Feeding recombinant Royalactin: Measures of improved lifespan and mitochondrial function in Caenorhabditis elegans

10.1101/2020.09.14.296053 ◽

2020 ◽

Author(s):

Xia Li ◽

Thomas L. Ingram ◽

Ying Wang ◽

Kamila Derecka ◽

Nathan Courtier ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Mitochondrial Function ◽

Royal Jelly ◽

Biological Functions ◽

C Elegans ◽

Beneficial Effects ◽

Physiological Processes ◽

Royal Jelly Protein ◽

Insight Into ◽

Over Time

AbstractAgeing, the decline of biological functions over time, is inherent to eukaryotes. Female honeybees attain a long-lived queen phenotype upon continuous consumption of royal jelly, whereas restricted supply of this nutritional substance promotes the development of worker bees, which are short-lived. An abundant protein found within royal jelly is major royal jelly protein 1 (MRJP1), also known as ‘Royalactin’. Health- and lifespan promoting effects have been attributed to Royalactin in species from diverse animal taxa, suggesting it acts on phylogenetically conserved physiological processes. Here, we explore the effects of feeding the nematode Caenorhabditis elegans with Escherichia coli that express a recombinant form of Royalactin (RArec). We confirm that consumption of RArec increases body size, improves locomotion and extends lifespan. We discover a link between Royalactin and mitochondria, organelles which play a key part in the ageing process: both spare respiratory capacity and morphology indicate improved mitochondrial function in RArec fed C. elegans. These results demonstrate the feasibility of using recombinant Royalactin to gain further insight into processes of healthy ageing in many species.RArec production allows insight into potential beneficial effects across species.

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Lnc2Cancer 3.0: an updated resource for experimentally supported lncRNA/circRNA cancer associations and web tools based on RNA-seq and scRNA-seq data

Nucleic Acids Research ◽

10.1093/nar/gkaa1006 ◽

2020 ◽

Vol 49 (D1) ◽

pp. D1251-D1258

Author(s):

Yue Gao ◽

Shipeng Shang ◽

Shuang Guo ◽

Xin Li ◽

Hanxiao Zhou ◽

...

Keyword(s):

Genetic Variants ◽

Regulatory Mechanisms ◽

Circular Rnas ◽

Rna Seq ◽

Biological Functions ◽

Cancer Subtypes ◽

Web Tools ◽

Online Tools ◽

Non Coding Rnas ◽

Mesenchymal Transformation

Abstract An updated Lnc2Cancer 3.0 (http://www.bio-bigdata.net/lnc2cancer or http://bio-bigdata.hrbmu.edu.cn/lnc2cancer) database, which includes comprehensive data on experimentally supported long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) associated with human cancers. In addition, web tools for analyzing lncRNA expression by high-throughput RNA sequencing (RNA-seq) and single-cell RNA-seq (scRNA-seq) are described. Lnc2Cancer 3.0 was updated with several new features, including (i) Increased cancer-associated lncRNA entries over the previous version. The current release includes 9254 lncRNA-cancer associations, with 2659 lncRNAs and 216 cancer subtypes. (ii) Newly adding 1049 experimentally supported circRNA-cancer associations, with 743 circRNAs and 70 cancer subtypes. (iii) Experimentally supported regulatory mechanisms of cancer-related lncRNAs and circRNAs, involving microRNAs, transcription factors (TF), genetic variants, methylation and enhancers were included. (iv) Appending experimentally supported biological functions of cancer-related lncRNAs and circRNAs including cell growth, apoptosis, autophagy, epithelial mesenchymal transformation (EMT), immunity and coding ability. (v) Experimentally supported clinical relevance of cancer-related lncRNAs and circRNAs in metastasis, recurrence, circulation, drug resistance, and prognosis was included. Additionally, two flexible online tools, including RNA-seq and scRNA-seq web tools, were developed to enable fast and customizable analysis and visualization of lncRNAs in cancers. Lnc2Cancer 3.0 is a valuable resource for elucidating the associations between lncRNA, circRNA and cancer.

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Circular RNAs in osteoarthritis: indispensable regulators and novel strategies in clinical implications

Arthritis Research & Therapy ◽

10.1186/s13075-021-02420-2 ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

Wenchao Zhang ◽

Lin Qi ◽

Ruiqi Chen ◽

Jieyu He ◽

Zhongyue Liu ◽

...

Keyword(s):

Hot Spot ◽

Circular Rnas ◽

Clinical Implications ◽

Biological Processes ◽

Future Directions ◽

The Past ◽

Prevalent Disease ◽

Post Traumatic ◽

Socioeconomic Burden ◽

Insight Into

AbstractOver the past decades, circular RNAs (circRNAs) have emerged as a hot spot and sparked intensive interest. Initially considered as the transcriptional noises, further studies have indicated that circRNAs are crucial regulators in multiple cellular biological processes, and thus engage in the development and progression of many diseases including osteoarthritis (OA). OA is a prevalent disease that mainly affects those aging, obese and post-traumatic population, posing as a major source of socioeconomic burden. Recently, numerous circRNAs have been found aberrantly expressed in OA tissues compared with counterparts. More importantly, circRNAs have been demonstrated to interplay with components in OA microenvironments, such as chondrocytes, synoviocytes and macrophages, by regulation of their proliferation, apoptosis, autophagy, inflammation, or extracellular matrix reorganization. Herein, in this review, we extensively summarize the roles of circRNAs in OA microenvironment, progression, and putative treatment, as well as envision the future directions for circRNAs research in OA, with the aim to provide a novel insight into this field.

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Parsimonious scenario for the emergence of viroid-like repliconsde novo

10.1101/593640 ◽

2019 ◽

Author(s):

Pablo Catalán ◽

Santiago F. Elena ◽

José A. Cuesta ◽

Susanna Manrubia

Keyword(s):

De Novo ◽

Rna World ◽

Circular Rna ◽

Biochemical Properties ◽

Circular Rnas ◽

Sequence Motifs ◽

Rna Sequences ◽

Specific Sequence ◽

Evolutionary Pathway ◽

Rna Molecules

AbstractViroids are small, non-coding, circular RNA molecules that infect plants. Different hypotheses for their evolutionary origin have been put forward, such as an early emergence in a precellular RNA World or severalde novoindependent evolutionary origins in plants. Here we discuss the plausibility ofde novoemergence of viroid-like replicons by giving theoretical support to the likelihood of different steps along a parsimonious evolutionary pathway. While Avsunviroidae-like structures are relatively easy to obtain through evolution of a population of random RNA sequences of fixed length, rod-like structures typical of Pospiviroidae are difficult to fix. Using different quantitative approaches, we evaluate the likelihood that RNA sequences fold into a rod-like structure and bear specific sequence motifs facilitating interactions with other molecules,e.g.RNA polymerases, RNases and ligases. By means of numerical simulations, we show that circular RNA replicons analogous to Pospiviroidae emerge if evolution is seeded with minimal circular RNAs that grow through the gradual addition of nucleotides. Further, these rod-like replicons often maintain their structure if independent functional modules are acquired that impose selective constraints. The evolutionary scenario we propose here is consistent with the structural and biochemical properties of viroids described to date.

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