scholarly journals FUCHS - Towards full circular RNA characterization using RNAseq

2016 ◽  
Author(s):  
Franziska Metge ◽  
Lisa F Czaja-Hasse ◽  
Richard Reinhardt ◽  
Chistoph Dieterich
Keyword(s):  
Splice Site ◽  
Developmental Stages ◽  
Computational Prediction ◽  
Break Point ◽  
Circular Rna ◽  
Circular Rnas ◽  
Functional Studies ◽  
Long Reads ◽  
Mirna Sponges ◽  
Rna Maturation

Circular RNAs (circRNAs) belong to a recently re-discovered species of RNA that emerge during RNA maturation through a process called back-splicing. A downstream 5’ splice site is linked to an upstream 3’ splice site to form a circular transcript instead of a canonical linear transcript. Recent advances in next-generation sequencing (NGS) have brought circRNAs back into the focus of many scientists. Since then, several studies reported that circRNAs are differentially expressed across tissue types and developmental stages, implying that they are actively regulated and not merely a by-product of splicing. Though functional studies have shown that some circRNAs could act as miRNA-sponges, the function of most circRNAs remains unknown. To expand our understanding of possible roles of circular RNAs, we propose a new pipeline that could fully characterizes candidate circRNA structure from RNAseq data – FUCHS: FUll CHaracterization of circular RNA using RNA- Sequencing. Currently, most computational prediction pipelines use back-spliced reads to identify circular RNAs. FUCHS extends this concept by considering all RNA-seq information from long reads (typically > 150 bp) to learn more about the exon coverage, the number of double break point fragments, the different circular isoforms arising from one host-gene, and the alternatively spliced exons within the same circRNA boundaries. This new knowledge will enable the user to carry out differential-motif enrichment and miRNA-seed analysis to determine potential regulators during circRNA biogenesis. FUCHS is an easy-to-use Python based pipeline that contributes a new aspect to the circRNA research. The pipeline is available as git repository: https://github.com/dieterich-lab/FUCHS

scholarly journals FUCHS - Towards full circular RNA characterization using RNAseq

2016 ◽  
Author(s):  
Franziska Metge ◽  
Lisa F Czaja-Hasse ◽  
Richard Reinhardt ◽  
Chistoph Dieterich
Keyword(s):  
Splice Site ◽  
Developmental Stages ◽  
Computational Prediction ◽  
Break Point ◽  
Circular Rna ◽  
Circular Rnas ◽  
Functional Studies ◽  
Long Reads ◽  
Mirna Sponges ◽  
Rna Maturation

Circular RNAs (circRNAs) belong to a recently re-discovered species of RNA that emerge during RNA maturation through a process called back-splicing. A downstream 5’ splice site is linked to an upstream 3’ splice site to form a circular transcript instead of a canonical linear transcript. Recent advances in next-generation sequencing (NGS) have brought circRNAs back into the focus of many scientists. Since then, several studies reported that circRNAs are differentially expressed across tissue types and developmental stages, implying that they are actively regulated and not merely a by-product of splicing. Though functional studies have shown that some circRNAs could act as miRNA-sponges, the function of most circRNAs remains unknown. To expand our understanding of possible roles of circular RNAs, we propose a new pipeline that could fully characterizes candidate circRNA structure from RNAseq data – FUCHS: FUll CHaracterization of circular RNA using RNA- Sequencing. Currently, most computational prediction pipelines use back-spliced reads to identify circular RNAs. FUCHS extends this concept by considering all RNA-seq information from long reads (typically > 150 bp) to learn more about the exon coverage, the number of double break point fragments, the different circular isoforms arising from one host-gene, and the alternatively spliced exons within the same circRNA boundaries. This new knowledge will enable the user to carry out differential-motif enrichment and miRNA-seed analysis to determine potential regulators during circRNA biogenesis. FUCHS is an easy-to-use Python based pipeline that contributes a new aspect to the circRNA research. The pipeline is available as git repository: https://github.com/dieterich-lab/FUCHS

scholarly journals FUCHS—towards full circular RNA characterization using RNAseq

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e2934 ◽  
Author(s):  
Franziska Metge ◽  
Lisa F. Czaja-Hasse ◽  
Richard Reinhardt ◽  
Chistoph Dieterich
Keyword(s):  
Splice Site ◽  
Developmental Stages ◽  
Computational Prediction ◽  
Break Point ◽  
Circular Rna ◽  
Circular Rnas ◽  
Functional Studies ◽  
Long Reads ◽  
Mirna Sponges ◽  
Rna Maturation

Circular RNAs (circRNAs) belong to a recently re-discovered species of RNA that emerge during RNA maturation through a process called back-splicing. A downstream 5′ splice site is linked to an upstream 3′ splice site to form a circular transcript instead of a canonical linear transcript. Recent advances in next-generation sequencing (NGS) have brought circRNAs back into the focus of many scientists. Since then, several studies reported that circRNAs are differentially expressed across tissue types and developmental stages, implying that they are actively regulated and not merely a by-product of splicing. Though functional studies have shown that some circRNAs could act as miRNA-sponges, the function of most circRNAs remains unknown. To expand our understanding of possible roles of circular RNAs, we propose a new pipeline that could fully characterizes candidate circRNA structure from RNAseq data—FUCHS: FUll CHaracterization of circular RNA using RNA-Sequencing. Currently, most computational prediction pipelines use back-spliced reads to identify circular RNAs. FUCHS extends this concept by considering all RNA-seq information from long reads (typically >150 bp) to learn more about the exon coverage, the number of double break point fragments, the different circular isoforms arising from one host-gene, and the alternatively spliced exons within the same circRNA boundaries. This new knowledge will enable the user to carry out differential motif enrichment and miRNA seed analysis to determine potential regulators during circRNA biogenesis. FUCHS is an easy-to-use Python based pipeline that contributes a new aspect to the circRNA research.

scholarly journals The effective function of circular RNA in colorectal cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mandana Ameli-Mojarad ◽  
Melika Ameli-Mojarad ◽  
Mahrooyeh Hadizadeh ◽  
Chris Young ◽  
Hosna Babini ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Circular Rna ◽  
Circular Rnas ◽  
Colorectal Tumorigenesis ◽  
Non Coding Rnas ◽  
Mirna Sponges ◽  
Mechanisms Of Development

AbstractColorectal cancer (CRC) is the 3rd most common type of cancer worldwide. Late detection plays role in one-third of annual mortality due to CRC. Therefore, it is essential to find a precise and optimal diagnostic and prognostic biomarker for the identification and treatment of colorectal tumorigenesis. Covalently closed, circular RNAs (circRNAs) are a class of non-coding RNAs, which can have the same function as microRNA (miRNA) sponges, as regulators of splicing and transcription, and as interactors with RNA-binding proteins (RBPs). Therefore, circRNAs have been investigated as specific targets for diagnostic and prognostic detection of CRC. These non-coding RNAs are also linked to metastasis, proliferation, differentiation, migration, angiogenesis, apoptosis, and drug resistance, illustrating the importance of understanding their involvement in the molecular mechanisms of development and progression of CRC. In this review, we present a detailed summary of recent findings relating to the dysregulation of circRNAs and their potential role in CRC.

scholarly journals The Regulatory Functions of Circular RNAs in Digestive System Cancers

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 770 ◽  
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.

scholarly journals Gammaherpesvirus RNAs Come Full Circle

mBio ◽  
2019 ◽  
Vol 10 (2) ◽  
Author(s):  
Nathan A. Ungerleider ◽  
Scott A. Tibbetts ◽  
Rolf Renne ◽  
Erik K. Flemington
Keyword(s):  
Adaptive Immune Response ◽  
Noncoding Rnas ◽  
Viral Gene Expression ◽  
Circular Rna ◽  
Circular Rnas ◽  
Viral Gene ◽  
Functional Studies ◽  
Barr Virus ◽  
Epstein Barr ◽  
Gammaherpesvirus 68

ABSTRACTAfter an adaptive immune response is mounted, gammaherpesviruses achieve persistence through the utilization of viral noncoding RNAs to craft a suitable host cell environment in an immunologically transparent manner. While gammaherpesvirus long noncoding RNAs (lncRNAs) and microRNAs have been recognized for some time and have been actively investigated, a recent spate of reports have now identified repertoires of the circular RNA (circRNA) class of noncoding RNAs in both the lymphocryptovirus and rhadinovirus genera of gammaherpesviruses. Despite the recent nature of these findings, the detection of circRNAs across viruses and viral gene expression programs, the conservation of some viral circRNAs, and their detection in the clinical setting already raises the spectrum of functional importance in gammaherpesvirus biology and associated malignancies. Here, we provide an overview of currently known gammaherpesvirus circular RNAs and discuss reported physical and contextual properties that may be germane to future functional studies. With the Epstein-Barr virus (EBV) circRNAome being the most extensively studied to date, our discussions will be weighted toward EBV circRNAs while also addressing circRNAs discovered in the rhesus macaque lymphocryptovirus (rLCV), the Kaposi’s sarcoma herpesvirus (KSHV), and the murid gammaherpesvirus 68 (MHV68). We hope that this will help set the stage for future investigations into the functions and relevance of this new class of viral noncoding RNAs in infection and disease.

scholarly journals Potential Significance of Circular RNA in Human Placental Tissue for Patients with Preeclampsia

2016 ◽  
Vol 39 (4) ◽  
pp. 1380-1390 ◽  
Author(s):  
Yating Qian ◽  
Yuanqing Lu ◽  
Can Rui ◽  
Yujia Qian ◽  
Manhong Cai ◽  
...  
Keyword(s):  
Operating Characteristic ◽  
Placental Tissue ◽  
Circular Rna ◽  
Circular Rnas ◽  
Potential Significance ◽  
Human Placental Tissue ◽  
Polymerase Chain ◽  
Mirna Sponges ◽  
Basic Content ◽  
Experimental Group

Aims: This study aimed to identify the different expression of circular RNAs (circRNAs) in the placental tissues of pregnant women with preeclampsia (PE) and to provide a new avenue of research regarding the pathological mechanisms of PE. Methods: In this study, we collected 40 placental tissues from PE patients and 35 placental tissues from gestational age-matched patients who gave premature birth. Arraystar circRNA Microarray Technology (KANGCHEN, Shanghai, China) was used to analyze the differential expression of circRNAs. According to the basic content of circRNAs in the two groups and their fold changes and due to the practicability of the designed divergent primers of each candidate circRNA, we selected three up-regulated circRNAs, hsa_circRNA_100782, hsa_circRNA_102682 and hsa_circRNA_104820, to validate the data. Real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was utilized to estimate the Ct values in both groups. We further evaluated the differences with a paired t-test and a receiver operating characteristic (ROC) curve. Results: Many circRNAs were found to be differentially expressed in PE placental tissues versus their controls; of these, 143 circRNAs were up-regulated and 158 were down-regulated. The expression levels of hsa_circRNA_100782 (p < 0.05), hsa_circRNA_102682 (p < 0.05), and hsa_circRNA_104820 (p < 0.0001) were validated as significantly up-regulated in the experimental group compared with the controls. Finally, we performed a literature comparison to forecast the possible mechanisms of circRNA function during PE. Conclusion: circRNA expression significantly differed in placental PE tissues compared with controls. According to the circRNA microarray results and the existing papers, circRNAs may contribute to the pathogenesis of PE by acting as miRNA sponges; this possibility requires additional investigation in future studies.

scholarly journals Circular RNAs in Cardiovascular Disease: An Overview

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Ximin Fan ◽  
Xinyu Weng ◽  
Yifan Zhao ◽  
Wei Chen ◽  
Tianyi Gan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Noncoding Rna ◽  
Essential Role ◽  
Closed Loop ◽  
Regulation Of Gene Expression ◽  
Circular Rna ◽  
Circular Rnas ◽  
Mirna Sponges

Circular RNA (circRNA), a novel type of endogenous noncoding RNA (ncRNA), has become a research hotspot in recent years. CircRNAs are abundant and stably exist in creatures, and they are found with covalently closed loop structures in which they are quite different from linear RNAs. Nowadays, an increasing number of scientists have demonstrated that circRNAs may have played an essential role in the regulation of gene expression, especially acting as miRNA sponges, and have described the potential mechanisms of several circRNAs in diseases, hinting at their clinical therapeutic values. In this review, the authors summarized the current understandings of the biogenesis and properties of circRNAs and their functions and role as biomarkers in cardiovascular diseases.

scholarly journals Functions of Circular RNAs Involved in Animal Skeletal Muscle Development – A Review

2020 ◽  
Vol 20 (1) ◽  
pp. 3-10
Author(s):  
Patricia Adu-Asiamah ◽  
Qiying Leng ◽  
Haidong Xu ◽  
Jiahui Zheng ◽  
Zhihui Zhao ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Growth And Development ◽  
Molecular Mechanisms ◽  
Muscle Development ◽  
Developmental Stages ◽  
Expression Patterns ◽  
Vital Role ◽  
Circular Rnas ◽  
Cell Proliferation And Differentiation ◽  
Mirna Sponges

AbstractCircular RNAs (circRNAs) have been identified in the skeletal muscle of numerous species of animals. Their abundance, diversity, and their dynamic expression patterns have been revealed in various developmental stages and physiological conditions in skeletal muscles. Recently, studies have made known that circRNAs widely participate in muscle cell proliferation and differentiation. They are also involved in other life processes such as functioning as microRNA (miRNA) sponges, regulators of splicing and transcription, and modifiers of parental gene expression with emerging pieces of evidence indicating a high chance of playing a vital role in several cells and tissues, especially the muscles. Other research has emphatically stated that the growth and development of skeletal muscle are regulated by proteins as well as non-coding RNAs, which involve circRNAs. Therefore, circRNAs have been considered significant biological regulators for understanding the molecular mechanisms of myoblasts. Here, we discuss how circRNAs are abundantly expressed in muscle (myoblast) and their critical roles in growth and development.

scholarly journals A genome-wide circular RNA transcriptome in Rat

2021 ◽  
Author(s):  
Disha Sharma ◽  
Paras Sehgal ◽  
Sridhar Sivasubbu ◽  
Vinod Scaria
Keyword(s):  
Developmental Stages ◽  
Donor Site ◽  
Model Organism ◽  
Circular Rna ◽  
Model Organisms ◽  
Circular Rnas ◽  
Acceptor Site ◽  
Tissue Samples ◽  
A Genome ◽  
The Difference

AbstractBackgroundCircular RNAs are a novel class of non-coding RNAs that backsplice from 5’ donor site and 3’ acceptor site to form a circular structure. A number of circRNAs have been discovered in model organisms including human, mouse, Drosophila, among other organisms. There are a few candidate-based studies on circular RNAs in rat, a well studied model organism. The availability of a recent dataset of transcriptomes encompassing 11 tissues, 4 developmental stages and 2 genders motivated us to explore the landscape of circular RNAs in the organism.MethodologyIn order to understand the difference among different pipelines, we have used the same bodymap RNA sequencing dataset. A number of pipelines have been published to identify the backsplice junctions for the discovery of circRNAs but studies comparing these tools have suggested that a combination of tools would be a better approach to identify high-confidence circular RNAs. We employed 5 different combinations of tools including tophat_CIRCexplorer2, segemehl_CIRCexplorer2, star_CIRCexplorer, Bowtie2_findcirc and Bowtie2_findcirc (noHisat2) to identify circular RNAs from the dataset.ResultsOur analysis identified a number of tissue-specific, developmental stage specific and gender specific circular RNAs. We further independently validated 16 circRNA junctions out of 24 selected candidates in 5 tissue samples. We additionally estimated the quantitative expression of 5 circRNA candidates using real-time PCR and our analysis suggests 3 candidates as tissue-enrichedConclusionThis study is one of the most comprehensive studies that provides a circular RNA transcriptome as well as to understand the difference among different computational pipelines in Rat.

scholarly journals Circular RNA MCTP2 inhibits cisplatin resistance in gastric cancer by miR-99a-5p-mediated induction of MTMR3 expression

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Guangli Sun ◽  
Zheng Li ◽  
Zhongyuan He ◽  
Weizhi Wang ◽  
Sen Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Xenograft Model ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Mouse Xenograft Model ◽  
Mirna Sponges ◽  
High Level

Abstract Background Cisplatin (CDDP) is the first-line chemotherapy for gastric cancer (GC). The poor prognosis of GC patients is partially due to the development of CDDP resistance. Circular RNAs (circRNAs) are a subclass of noncoding RNAs that function as microRNA (miRNA) sponges. The role of circRNAs in CDDP resistance in GC has not been evaluated. Methods RNA sequencing was used to identify the differentially expressed circRNAs between CDDP-resistant and CDDP-sensitive GC cells. qRT-PCR was used to detect the expression of circMCTP2 in GC tissues. The effects of circMCTP2 on CDDP resistance were investigated in vitro and in vivo. Pull-down assays and luciferase reporter assays were performed to confirm the interactions among circMCTP2, miR-99a-5p, and myotubularin-related protein 3 (MTMR3). The protein expression levels of MTMR3 were detected by western blotting. Autophagy was evaluated by confocal microscopy and transmission electron microscopy (TEM). Results CircMCTP2 was downregulated in CDDP-resistant GC cells and tissues compared to CDDP-sensitive GC cells and tissues. A high level of circMCTP2 was found to be a favorable factor for the prognosis of patients with GC. CircMCTP2 inhibited proliferation while promoting apoptosis of CDDP-resistant GC cells in response to CDDP treatment. CircMCTP2 was also found to reduce autophagy in CDDP-resistant GC cells. MiR-99a-5p was verified to be sponged by circMCTP2. Inhibition of miR-99a-5p could sensitize GC cells to CDDP. MTMR3 was confirmed to be a direct target of miR-99a-5p. Knockdown of MTMR3 reversed the effects of circMCTP2 on the proliferation, apoptosis and autophagy of CDDP-resistant GC cells. CircMCTP2 was also confirmed to inhibit CDDP resistance in vivo in a nude mouse xenograft model. Conclusions CircMCTP2 sensitizes GC to CDDP through the upregulation of MTMR3 by sponging miR-99a-5p. Overexpression of CircMCTP2 could be a new therapeutic strategy for counteracting CDDP resistance in GC.

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