scholarly journals Comparative Analysis of Gammaherpesvirus Circular RNA Repertoires: Conserved and Unique Viral Circular RNAs

2018 ◽  
Vol 93 (6) ◽  
Author(s):  
Nathan A. Ungerleider ◽  
Vaibhav Jain ◽  
Yiping Wang ◽  
Nicholas J. Maness ◽  
Robert V. Blair ◽  
...  
Keyword(s):  
Rhesus Macaque ◽  
Noncoding Rnas ◽  
Circular Rna ◽  
Circular Rnas ◽  
Infection Model ◽  
Host Immune System ◽  
Immune Recognition ◽  
Origin Of Replication ◽  
Two Samples ◽  
Virus Biology

ABSTRACTRecent studies have identified circular RNAs (circRNAs) expressed from the Epstein-Barr virus (EBV) and Kaposi’s sarcoma herpesvirus (KSHV) human DNA tumor viruses. To gain initial insights into the potential relevance of EBV circRNAs in virus biology and disease, we assessed the circRNAome of the interspecies homologue rhesus macaque lymphocryptovirus (rLCV) in a naturally occurring lymphoma from a simian immunodeficiency virus (SIV)-infected rhesus macaque. This analysis revealed rLCV orthologues of the latency-associated EBV circular RNAs circRPMS1_E4_E3a and circEBNA_U. Also identified in two samples displaying unusually high lytic gene expression was a novel rLCV circRNA that contains both conserved and rLCV-specific RPMS1 exons and whose backsplice junctions flank an rLCV lytic origin of replication (OriLyt). Analysis of a lytic infection model for the murid herpesvirus 68 (MHV68) rhadinovirus identified a cluster of circRNAs near an MHV68 lytic origin of replication, with the most abundant of these, circM11_ORF69, spanning the OriLyt. Lastly, analysis of KSHV latency and reactivation models revealed the latency associated circRNA originating from the vIRF4 gene as the predominant viral circRNA. Together, the results of this study broaden our appreciation for circRNA repertoires in theLymphocryptovirusandRhadinovirusgenera of gammaherpesviruses and provide evolutionary support for viral circRNA functions in latency and viral replication.IMPORTANCEInfection with oncogenic gammaherpesviruses leads to long-term viral persistence through a dynamic interplay between the virus and the host immune system. Critical for remodeling of the host cell environment after the immune responses are viral noncoding RNAs that modulate host signaling pathways without attracting adaptive immune recognition. Despite the importance of noncoding RNAs in persistent infection, the circRNA class of noncoding RNAs has only recently been identified in gammaherpesviruses. Accordingly, their roles in virus infection and associated oncogenesis are unknown. Here we report evolutionary conservation of EBV-encoded circRNAs determined by assessing the circRNAome in rLCV-infected lymphomas from an SIV-infected rhesus macaque, and we report latent and lytic circRNAs from KSHV and MHV68. These experiments demonstrate utilization of the circular RNA class of RNAs across 4 members of the gammaherpesvirus subfamily, and they identify orthologues and potential homoplastic circRNAs, implying conserved circRNA functions in virus biology and associated malignancies.

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

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.

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 Circular RNA circFAT1(e2) Promotes Osteosarcoma Progression and Metastasis by Sponging miR-181b and Regulating HK2 Expression

2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
Huijie Gu ◽  
Xiangyang Cheng ◽  
Jun Xu ◽  
Kaifeng Zhou ◽  
Chong Bian ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cancer Progression ◽  
Therapeutic Target ◽  
Critical Role ◽  
Noncoding Rnas ◽  
Circular Rna ◽  
Expression Level ◽  
Circular Rnas ◽  
Competing Endogenous Rna ◽  
Potential Therapeutic Target

As a subclass of noncoding RNAs, circular RNAs (circRNAs) have been demonstrated to play a critical role in regulating gene expression in eukaryotes. Recent studies have revealed the pivotal functions of circRNAs in cancer progression. Nevertheless, how circRNAs participate in osteosarcoma (OS) development and progression are not well understood. In the present study, we identified a circRNA circFAT1(e2) with an upregulated expression level in OS tissues. By functional experiments, we found that circFAT1(e2) depletion significantly suppressed the proliferation and reduced migration in OS. In terms of mechanism, we found that circFAT1(e2) inhibited miR-181b, while miR-181b targeted HK2. By releasing the inhibition of miR-181b on HK2 expression, leading to attenuated OS progression. Mechanistic investigations suggested that circFAT1(e2) served as a competing endogenous RNA (ceRNA) of miR-181b to enhance HK2 expression. On the whole, our study indicated that circFAT1(e2) exerted oncogenic roles in OS and suggested the circFAT1(e2)/miR-181b/HK2 axis might be a potential therapeutic target.

scholarly journals A novel circular RNA, circXPO1, promotes lung adenocarcinoma progression by interacting with IGF2BP1

2020 ◽  
Vol 11 (12) ◽  
Author(s):  
Qi Huang ◽  
Haifa Guo ◽  
Shaodong Wang ◽  
Yi Ma ◽  
Haiming Chen ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Therapeutic Target ◽  
Noncoding Rnas ◽  
Xenograft Model ◽  
Gene Copy Number ◽  
Circular Rna ◽  
Gene Copy ◽  
Circular Rnas ◽  
Functional Roles ◽  
Tumor Tissues

AbstractStudies have demonstrated that noncoding RNAs play important roles in various types of cancer; however, noncoding RNAs derived from regions of genomic alterations have rarely been explored, especially for circular RNAs (circRNA). Previously, we found several circRNAs were upregulated in lung adenocarcinoma (LUAD) tumor tissues by RNA sequencing. Here, we characterized a novel circRNA, circXPO1, in LUAD, which is derived from a well-established cancer therapeutic target, XPO1. circXPO1, is formed by back-splicing of exon 3 and exon 4 of XPO1 gene. circXPO1 was highly expressed in LUAD tissues compared with paired adjacent non-tumor tissues, and high circXPO1 expression correlated with worse overall survival. circXPO1 expression was positively correlated with the XPO1 gene copy number. Mechanically, circXPO1 could bind with IGF2BP1 and enhance CTNNB1 mRNA stability, and subsequently promote LUAD progression. In a LUAD patient-derived xenograft model, intratumoural injection of cholesterol-conjugated siRNA specifically targeting circXPO1 efficiently suppressed tumor growth. To summary, these results suggest that circXPO1 is critical for LUAD progression and may serve as a biomarker for poor prognosis and a therapeutic target. On the other hand, the functional roles of noncoding transcripts derived from coding genes should be re-evaluated.

scholarly journals Circular RNA: biogenesis, degradation, functions and potential roles in mediating resistance to anticarcinogens

Epigenomics ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 267-283 ◽  
Author(s):  
Xiuchao Geng ◽  
Youchao Jia ◽  
Yuhao Zhang ◽  
Liang Shi ◽  
Qiang Li ◽  
...  
Keyword(s):  
Noncoding Rnas ◽  
Circular Rna ◽  
Cancer Drug ◽  
Circular Rnas ◽  
Cancer Drug Resistance ◽  
Cancer Pathogenesis ◽  
Scientific Papers ◽  
Rna Biogenesis ◽  
And Function ◽  
The Relationship

Aim: This review aims to systematically describe the biogenesis and degradation of circular RNAs (circRNAs), discusses the major functions of circRNAs, introduces the mechanisms by which circRNAs play a role in cancer, comprehensively summarize the relationship between circRNAs and anticarcinogen resistance as well as underlying specific mechanisms in multiple cancers. Materials & methods: We screened and analyzed large quantity of scientific papers which associated with circRNAs, noncoding RNAs, function, cancer, drug resistance and chemoresistance, and then summarized in Figures 1 & 2 & Table 1. Results & conclusion: The biogenesis, degradation and function of circRNAs are specially compared with other noncoding RNAs, it can affect cancer pathogenesis and progression and are implicated in mediating resistance to various anticarcinogens in various types of cancer.

scholarly journals Cancer-related circular RNA: diverse biological functions

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dan Cheng ◽  
Jing Wang ◽  
Zigang Dong ◽  
Xiang Li
Keyword(s):  
Noncoding Rnas ◽  
Circular Rna ◽  
Long Noncoding Rnas ◽  
Circular Rnas ◽  
Biological Functions ◽  
Diagnosis Of Cancer ◽  
The Relationship ◽  
Potential Biomarkers

AbstractNoncoding RNAs, including long noncoding RNAs (lncRNAs), microRNAs (miRNAs) and circular RNAs (circRNAs), are involved in regulating biological functions. In recent decades, miRNAs and lncRNAs have both inspired a wave of research, but the study of circRNA functions is still in its infancy. Studies have found that circRNAs actively participate in the occurrence and development of various diseases, which emphasizes the importance of circRNAs. Here, we review the features and classification of circRNAs and summarize their functions. Then, we briefly describe how to analyze circRNAs by bioinformatics procedures. In addition, the relationship between circRNAs and cancers is discussed with an emphasis on proving whether circRNAs can be potential biomarkers for the prognosis and diagnosis of cancer.

scholarly journals Biosynthesis of Circular RNA ciRS-7/CDR1as Is Mediated by Mammalian-Wide Interspersed Repeats (MIRs)

2018 ◽  
Author(s):  
Rei Yoshimoto ◽  
Karim Rahimi ◽  
Thomas Hansen ◽  
Jørgen Kjems ◽  
Akila Mayeda
Keyword(s):  
Noncoding Rnas ◽  
Circular Rna ◽  
Hek293 Cells ◽  
Circular Rnas ◽  
Inverted Repeats ◽  
Biosynthesis Pathway ◽  
Circular Structure ◽  
Reporter Assays ◽  
Interspersed Repeats

SUMMARYCircular RNAs (circRNAs) are stable noncoding RNAs with a closed circular structure. One of the first and best studied circRNAs is ciRS-7 (CDR1as) that acts as a regulator of the microRNA miR-7, however, the biosynthesis pathway has remained an enigma. Here we delineate the biosynthesis pathway of ciRS-7. The back-splicing events that form circRNAs are often facilitated by flanking inverted repeats of the primate-specific Alu elements. ciRS-7 gene lacks these elements but, instead, we identified a set of flanking inverted elements belonging to the mammalian-wide interspersed repeat (MIR) family. Splicing reporter assays in HEK293 cells demonstrated that these inverted MIRs are required to generate ciRS-7 through a back-splicing and CRISPR/Cas9-mediated deletions confirmed the requirement of the endogenous MIR elements in SH-SY5Y cells. Using bioinformatics searches, we identified several other MIR-dependent circRNAs that we confirmed experimentally. We propose that MIR-mediated RNA circularization constitutes a new widespread biosynthesis principle for mammalian circRNAs.

scholarly journals WebCircRNA: Classifying the Circular RNA Potential of Coding and Noncoding RNA

Genes ◽  
2018 ◽  
Vol 9 (11) ◽  
pp. 536 ◽  
Author(s):  
Xiaoyong Pan ◽  
Kai Xiong ◽  
Christian Anthon ◽  
Poul Hyttel ◽  
Kristine Freude ◽  
...  
Keyword(s):  
Stem Cell ◽  
Noncoding Rna ◽  
Noncoding Rnas ◽  
Stem Cell Differentiation ◽  
Circular Rna ◽  
Circular Rnas ◽  
Cell Potential ◽  
Random Forest Models ◽  
Transcriptional Gene Regulation ◽  
Stem Cell Potential

Circular RNAs (circRNAs) are increasingly recognized to play crucial roles in post-transcriptional gene regulation including functioning as microRNA (miRNA) sponges or as wide-spread regulators, for example in stem cell differentiation. It is therefore highly relevant to identify if a transcript of interest can also function as a circRNA. Here, we present a user-friendly web server that predicts if coding and noncoding RNAs have circRNA isoforms and whether circRNAs are expressed in stem cells. The predictions are made by random forest models using sequence-derived features as input. The output scores are converted to fractiles, which are used to assess the circRNA and stem cell potential. The performances of the three models are reported as the area under the receiver operating characteristic (ROC) curve and are 0.82 for coding genes, 0.89 for long noncoding RNAs (lncRNAs) and 0.72 for stem cell expression. We present WebCircRNA for quick evaluation of human genes and transcripts for their circRNA potential, which can be essential in several contexts.

scholarly journals Comprehensive profiling analysis of the N6-methyladenosine-modified circular RNA transcriptome in cultured cells infected with Marek’s disease virus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aijun Sun ◽  
Rui Wang ◽  
Shuaikang Yang ◽  
Xiaojing Zhu ◽  
Ying Liu ◽  
...  
Keyword(s):  
Disease Virus ◽  
Cultured Cells ◽  
Circular Rna ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Circular Rnas ◽  
Marek’S Disease Virus ◽  
Marek’S Disease ◽  
Pathway Analyses ◽  
Profiling Analysis

AbstractMarek’s disease virus (MDV) induces severe immunosuppression and lymphomagenesis in the chicken, its natural host, and results in a condition that investigated the pathogenesis of MDV and have begun to focus on the expression profiling of circular RNAs (circRNAs). However, little is known about how the expression of circRNAs is referred to as Marek’s disease. Previous reports have is regulated during MDV replication. Here, we carried out a comprehensive profiling analysis of N6-methyladenosine (m6A) modification on the circRNA transcriptome in infected and uninfected chicken embryonic fibroblast (CEF) cells. Methylated RNA immunoprecipitation sequencing (MeRIP-Seq) revealed that m6A modification was highly conserved in circRNAs. Comparing to the uninfected group, the number of peaks and conserved motifs were not significantly different in cells that were infected with MDV, although reduced abundance of circRNA m6A modifications. However, gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses revealed that the insulin signaling pathway was associated with the regulation of m6A modified circRNAs in MDV infection. This is the first report to describe alterations in the transcriptome-wide profiling of m6A modified circRNAs in MDV-infected CEF cells.

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