scholarly journals A comprehensive review of circRNA: from purification and identification to disease marker potential

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5503 ◽  
Author(s):  
Sheng Xu ◽  
LuYu Zhou ◽  
Murugavel Ponnusamy ◽  
LiXia Zhang ◽  
YanHan Dong ◽  
...  

Circular RNA (circRNA) is an endogenous noncoding RNA with a covalently closed cyclic structure. Based on their components, circRNAs are divided into exonic circRNAs, intronic circRNAs, and exon-intron circRNAs. CircRNAs have well-conserved sequences and often have high stability due to their resistance to exonucleases. Depending on their sequence, circRNAs are involved in different biological functions, including microRNA sponge activity, modulation of alternative splicing or transcription, interaction with RNA-binding proteins, and rolling translation, and are a derivative of pseudogenes. CircRNAs are involved in the development of a variety of pathological conditions, such as cardiovascular diseases, diabetes, neurological diseases, and cancer. Emerging evidence has shown that circRNAs are likely to be new potential clinical diagnostic markers or treatments for many diseases. Here we describe circRNA research methods and biological functions, and discuss the potential relationship between circRNAs and disease progression.

2018 ◽  
Author(s):  
Sheng Xu ◽  
LuYu Zhou ◽  
Murugavel Ponnusamy ◽  
LiXia Zhang ◽  
Kun Wang

Circular RNA (CircRNA) is an endogenous noncoding RNA with covalently closed cyclic structure. It is divided into exonic circRNA, intronic circRNA and exon-intron circRNA, based on their components. CircRNAs are well conserved in sequence and abundantly expressed in a tissue specific manner. They have a high stability due to resistance to exonuclease. Depends on their sequence, they perform many biological function including microRNA sponging activity, modulation of alternative splicing or transcription, interaction with RNA binding proteins, rolling translation and derivative of pseudogenes. They are involved in the development of a variety pathological condition including cardiovascular disease, diabetes, neurological diseases and cancer. Emerging evidences show that circRNA are likely to be potential targets for new clinical diagnostic markers or treatment of many diseases. In this review, we have described the potential relationship between circRNA and disease progression, methods and databases of cyclic RNA.


2018 ◽  
Author(s):  
Sheng Xu ◽  
LuYu Zhou ◽  
Murugavel Ponnusamy ◽  
LiXia Zhang ◽  
Kun Wang

Circular RNA (CircRNA) is an endogenous noncoding RNA with covalently closed cyclic structure. It is divided into exonic circRNA, intronic circRNA and exon-intron circRNA, based on their components. CircRNAs are well conserved in sequence and abundantly expressed in a tissue specific manner. They have a high stability due to resistance to exonuclease. Depends on their sequence, they perform many biological function including microRNA sponging activity, modulation of alternative splicing or transcription, interaction with RNA binding proteins, rolling translation and derivative of pseudogenes. They are involved in the development of a variety pathological condition including cardiovascular disease, diabetes, neurological diseases and cancer. Emerging evidences show that circRNA are likely to be potential targets for new clinical diagnostic markers or treatment of many diseases. In this review, we have described the potential relationship between circRNA and disease progression, methods and databases of cyclic RNA.


Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 770 ◽  
Author(s):  
Xiao Yuan ◽  
Ya Yuan ◽  
Zhi He ◽  
Diyan Li ◽  
Bo Zeng ◽  
...  

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.


2021 ◽  
Author(s):  
Chen Chang ◽  
Gang Ma ◽  
Edwin Cheung ◽  
Andrew P. Hutchins

AbstractRNA N6-Methyladenosine (m6A) is the most abundant mRNA modification, and forms part of an epitranscriptomic system that modulates RNA function. RNA modifications can be reversibly catalyzed by several specific enzymes, and those modifications can be recognized by RNA binding proteins that in turn regulate biological processes. Although there are many reports demonstrating m6A participation in critical biological functions, this exploration has mainly been conducted through the global knockout or knockdown of the writers, erasers, or readers of m6A. Consequently, there is a lack of information about the role of m6A on single transcripts in biological processes, posing a challenge in understanding the biological functions of m6A. Here, we demonstrate a CRISPR/dCas13a-based RNA m6A-editor which can target mRNAs using single crRNA or multiple crRNAs array to methylate or demethylate m6A. We systematically assay its capabilities to enable the targeted rewriting of m6A dynamics, including modulation of circular RNA translation and transcript half-life. Finally, we demonstrate the utility of the system by specifically modulating XIST m6A levels, which can control X chromosome silencing and activation. Based on our editors, m6A on single and multiple transcripts can be modified to allow the exploration of the role of m6A on in biological processes.


2020 ◽  
Vol 14 (7) ◽  
pp. 563-571 ◽  
Author(s):  
Jamal Hallajzadeh ◽  
Elaheh Amirani ◽  
Hamed Mirzaei ◽  
Rana Shafabakhsh ◽  
Seyyed M Mirhashemi ◽  
...  

Melanoma is the most lethal form of skin cancer. New technologies have resulted in major advances in the diagnosis and treatment of melanoma and other cancer types. Recently, some studies have investigated the role of circular RNAs (circRNAs) in different cancers. CircRNAs are a member of long noncoding RNA family mainly formed through back-splicing and have a closed-loop structure. These molecules affect several biological and oncogenic cascades in diverse ways via acting as microRNA sponge, interacting with RNA-binding proteins and acting as a transcription regulator. In this review, we made an insight into the impact of circRNA dysregulation in the melanoma tumorigenesis based on the presented evidences.


2020 ◽  
Author(s):  
Lijuan Hou ◽  
Jin Xie ◽  
Yaoyao Wu ◽  
Jiaojiao Wang ◽  
Anqi Duan ◽  
...  

Abstract Background Only 1.5% of the human genome encodes proteins, while most of the remaining encodes noncoding RNAs (ncRNA). Many ncRNAs form structures and perform many important functions. Accurately identifying structured ncRNAs in the human genome and discovering their biological functions remain a major challenge. Results Here, we have established a pipeline (CM-line) with the following features for analyzing the large genomes of humans and other animals. First, we selected species with larger genetic distances to facilitate the discovery of covariations and compatible mutations. Second, we used CMfinder, which can generate useful alignments even with low sequence conservation. Third, we removed repetitive sequences and known structured ncRNAs to reduce the workload of CMfinder. Fourth, we used Infernal to find more representatives and refine the structure. We reported 11 classes of structured ncRNA candidates with significant covariations in humans. Functional analysis showed that these ncRNAs have variable functions. Some may regulate circadian clock genes through poly (A) signals (PAS); some may regulate the elongation factor (EEF1A) and the T-cell receptor signaling pathway by cooperating with RNA binding proteins. Conclusions By searching for important features of RNA structure from large genomes, the CM-line has revealed the existence of a variety of novel structured ncRNAs. Functional analysis provides evidence for the potential biological functions of some newly found ncRNA motifs. The pipeline we have established for the discovery of structured ncRNAs and the identification of their functions can also be applied to analyze other large genomes.


BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Lijuan Hou ◽  
Jin Xie ◽  
Yaoyao Wu ◽  
Jiaojiao Wang ◽  
Anqi Duan ◽  
...  

Abstract Background Only 1.5% of the human genome encodes proteins, while large part of the remaining encodes noncoding RNAs (ncRNA). Many ncRNAs form structures and perform many important functions. Accurately identifying structured ncRNAs in the human genome and discovering their biological functions remain a major challenge. Results Here, we have established a pipeline (CM-line) with the following features for analyzing the large genomes of humans and other animals. First, we selected species with larger genetic distances to facilitate the discovery of covariations and compatible mutations. Second, we used CMfinder, which can generate useful alignments even with low sequence conservation. Third, we removed repetitive sequences and known structured ncRNAs to reduce the workload of CMfinder. Fourth, we used Infernal to find more representatives and refine the structure. We reported 11 classes of structured ncRNA candidates with significant covariations in humans. Functional analysis showed that these ncRNAs may have variable functions. Some may regulate circadian clock genes through poly (A) signals (PAS); some may regulate the elongation factor (EEF1A) and the T-cell receptor signaling pathway by cooperating with RNA binding proteins. Conclusions By searching for important features of RNA structure from large genomes, the CM-line has revealed the existence of a variety of novel structured ncRNAs. Functional analysis suggests that some newly discovered ncRNA motifs may have biological functions. The pipeline we have established for the discovery of structured ncRNAs and the identification of their functions can also be applied to analyze other large genomes.


2021 ◽  
Vol 22 (6) ◽  
pp. 3262
Author(s):  
Shuailong Zheng ◽  
Xujia Zhang ◽  
Emmanuel Odame ◽  
Xiaoli Xu ◽  
Yuan Chen ◽  
...  

Circular RNA (circRNA) is a kind of novel endogenous noncoding RNA formed through back-splicing of mRNA precursor. The biogenesis, degradation, nucleus–cytoplasm transport, location, and even translation of circRNA are controlled by RNA-binding proteins (RBPs). Therefore, circRNAs and the chaperoned RBPs play critical roles in biological functions that significantly contribute to normal animal development and disease. In this review, we systematically characterize the possible molecular mechanism of circRNA–protein interactions, summarize the latest research on circRNA–protein interactions in muscle development and myocardial disease, and discuss the future application of circRNA in treating muscle diseases. Finally, we provide several valid prediction methods and experimental verification approaches. Our review reveals the significance of circRNAs and their protein chaperones and provides a reference for further study in this field.


2019 ◽  
Vol 19 (4) ◽  
pp. 255-263 ◽  
Author(s):  
Yuangang Wu ◽  
Xiaoxi Lu ◽  
Bin Shen ◽  
Yi Zeng

Background: Osteoarthritis (OA) is a disease characterized by progressive degeneration, joint hyperplasia, narrowing of joint spaces, and extracellular matrix metabolism. Recent studies have shown that the pathogenesis of OA may be related to non-coding RNA, and its pathological mechanism may be an effective way to reduce OA. Objective: The purpose of this review was to investigate the recent progress of miRNA, long noncoding RNA (lncRNA) and circular RNA (circRNA) in gene therapy of OA, discussing the effects of this RNA on gene expression, inflammatory reaction, apoptosis and extracellular matrix in OA. Methods: The following electronic databases were searched, including PubMed, EMBASE, Web of Science, and the Cochrane Library, for published studies involving the miRNA, lncRNA, and circRNA in OA. The outcomes included the gene expression, inflammatory reaction, apoptosis, and extracellular matrix. Results and Discussion: With the development of technology, miRNA, lncRNA, and circRNA have been found in many diseases. More importantly, recent studies have found that RNA interacts with RNA-binding proteins to regulate gene transcription and protein translation, and is involved in various pathological processes of OA, thus becoming a potential therapy for OA. Conclusion: In this paper, we briefly introduced the role of miRNA, lncRNA, and circRNA in the occurrence and development of OA and as a new target for gene therapy.


2021 ◽  
Vol 15 ◽  
Author(s):  
Lichao Zhang ◽  
Zihong Huang ◽  
Liang Kong

Background: RNA-binding proteins establish posttranscriptional gene regulation by coordinating the maturation, editing, transport, stability, and translation of cellular RNAs. The immunoprecipitation experiments could identify interaction between RNA and proteins, but they are limited due to the experimental environment and material. Therefore, it is essential to construct computational models to identify the function sites. Objective: Although some computational methods have been proposed to predict RNA binding sites, the accuracy could be further improved. Moreover, it is necessary to construct a dataset with more samples to design a reliable model. Here we present a computational model based on multi-information sources to identify RNA binding sites. Method: We construct an accurate computational model named CSBPI_Site, based on xtreme gradient boosting. The specifically designed 15-dimensional feature vector captures four types of information (chemical shift, chemical bond, chemical properties and position information). Results: The satisfied accuracy of 0.86 and AUC of 0.89 were obtained by leave-one-out cross validation. Meanwhile, the accuracies were slightly different (range from 0.83 to 0.85) among three classifiers algorithm, which showed the novel features are stable and fit to multiple classifiers. These results showed that the proposed method is effective and robust for noncoding RNA binding sites identification. Conclusion: Our method based on multi-information sources is effective to represent the binding sites information among ncRNAs. The satisfied prediction results of Diels-Alder riboz-yme based on CSBPI_Site indicates that our model is valuable to identify the function site.


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