Circular RNA–MicroRNA–MRNA interaction predictions in SARS-CoV-2 infection

Abstract Different types of noncoding RNAs like microRNAs (miRNAs) and circular RNAs (circRNAs) have been shown to take part in various cellular processes including post-transcriptional gene regulation during infection. MiRNAs are expressed by more than 200 organisms ranging from viruses to higher eukaryotes. Since miRNAs seem to be involved in host–pathogen interactions, many studies attempted to identify whether human miRNAs could target severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNAs as an antiviral defence mechanism. In this work, a machine learning based miRNA analysis workflow was developed to predict differential expression patterns of human miRNAs during SARS-CoV-2 infection. In order to obtain the graphical representation of miRNA hairpins, 36 features were defined based on the secondary structures. Moreover, potential targeting interactions between human circRNAs and miRNAs as well as human miRNAs and viral mRNAs were investigated.

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The Biomarker and Therapeutic Potential of Circular Rnas in Schizophrenia

Cells ◽

10.3390/cells9102238 ◽

2020 ◽

Vol 9 (10) ◽

pp. 2238

Author(s):

Artem Nedoluzhko ◽

Natalia Gruzdeva ◽

Fedor Sharko ◽

Sergey Rastorguev ◽

Natalia Zakharova ◽

...

Keyword(s):

Gene Expression ◽

Rna Binding ◽

Gene Expression Regulation ◽

Rna Binding Proteins ◽

Therapeutic Potential ◽

Expression Patterns ◽

Circular Rna ◽

Circular Rnas ◽

Cellular Processes ◽

Non Coding Rna

Circular RNAs (circRNAs) are endogenous, single-stranded, most frequently non-coding RNA (ncRNA) molecules that play a significant role in gene expression regulation. Circular RNAs can affect microRNA functionality, interact with RNA-binding proteins (RBPs), translate proteins by themselves, and directly or indirectly modulate gene expression during different cellular processes. The affected expression of circRNAs, as well as their targets, can trigger a cascade of events in the genetic regulatory network causing pathological conditions. Recent studies have shown that altered circular RNA expression patterns could be used as biomarkers in psychiatric diseases, including schizophrenia (SZ); moreover, circular RNAs together with other cell molecules could provide new insight into mechanisms of this disorder. In this review, we focus on the role of circular RNAs in the pathogenesis of SZ and analyze their biomarker and therapeutic potential in this disorder.

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Circular RNA repertoires are associated with evolutionarily young transposable elements

eLife ◽

10.7554/elife.67991 ◽

2021 ◽

Vol 10 ◽

Author(s):

Franziska Gruhl ◽

Peggy Janich ◽

Henrik Kaessmann ◽

David Gatfield

Keyword(s):

Transposable Elements ◽

Repetitive Sequences ◽

Purifying Selection ◽

Circular Rna ◽

Circular Rnas ◽

Orthologous Genes ◽

Transposon Insertion ◽

Orthologous Loci ◽

Transcriptional Gene Regulation ◽

Species Specific

Circular RNAs (circRNAs) are found across eukaryotes and can function in post-transcriptional gene regulation. Their biogenesis through a circle-forming backsplicing reaction is facilitated by reverse-complementary repetitive sequences promoting pre-mRNA folding. Orthologous genes from which circRNAs arise, overall contain more strongly conserved splice sites and exons than other genes, yet it remains unclear to what extent this conservation reflects purifying selection acting on the circRNAs themselves. Our analyses of circRNA repertoires from five species representing three mammalian lineages (marsupials, eutherians: rodents, primates) reveal that surprisingly few circRNAs arise from orthologous exonic loci across all species. Even the circRNAs from orthologous loci are associated with young, recently active and species-specific transposable elements, rather than with common, ancient transposon integration events. These observations suggest that many circRNAs emerged convergently during evolution - as a byproduct of splicing in orthologs prone to transposon insertion. Overall, our findings argue against widespread functional circRNA conservation.

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Expression Profile of Circular RNAs in Epicardial Adipose Tissue in Heart Failure

10.1101/764266 ◽

2019 ◽

Author(s):

Meili Zheng ◽

Lei Zhao ◽

Xinchun Yang

Keyword(s):

Heart Failure ◽

Adipose Tissue ◽

Expression Profile ◽

Epicardial Adipose Tissue ◽

Expression Profiles ◽

Expression Patterns ◽

Circular Rna ◽

Circular Rnas ◽

Artery Disease ◽

Pathway Analyses

AbstractRecent studies have reported circular RNA (circRNA) expression profiles in various tissue types; specifically, a recent work showed a detailed circRNA expression landscape in the heart. However, circRNA expression profile in human epicardial adipose tissue (EAT) remains undefined. RNA-sequencing was carried out to compare circRNA expression patterns in EAT specimens from coronary artery disease (CAD) cases between the heart failure (HF) and non-HF groups. The top highly expressed EAT circRNAs corresponded to genes involved in cell proliferation and inflammatory response, including KIAA0182, RHOBTB3, HIPK3, UBXN7, PCMTD1, N4BP2L2, CFLAR, EPB41L2, FCHO2, FNDC3B and SPECC1. Among the 141 circRNAs substantially different between the HF and non-HF groups (P<0.05;fold change>2), hsa_circ_0005565 stood out, and was mostly associated with positive regulation of metabolic processes and insulin resistancein GO and KEGG pathway analyses, respectively. These data indicate EAT circRNAs contribute to the pathogenesis of metabolic disorders causing HF.

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Circular RNA repertoires are associated with evolutionarily young transposable elements

10.1101/2021.03.01.433421 ◽

2021 ◽

Author(s):

Franziska Gruhl ◽

Peggy Janich ◽

Henrik Kaessmann ◽

David Gatfield

Keyword(s):

Transposable Elements ◽

Repetitive Sequences ◽

Purifying Selection ◽

Circular Rna ◽

Circular Rnas ◽

Transposable Element Insertion ◽

Orthologous Genes ◽

Orthologous Loci ◽

Transcriptional Gene Regulation ◽

Species Specific

AbstractCircular RNAs (circRNAs) are found across eukaryotes and can function in post-transcriptional gene regulation. Their biogenesis through a circle-forming backsplicing reaction is facilitated by reverse-complementary repetitive sequences promoting pre-mRNA folding. Orthologous genes from which circRNAs arise, overall contain more strongly conserved splice sites and exons than other genes, yet it remains unclear to what extent this conservation reflects purifying selection acting on the circRNAs themselves. Our analyses of circRNA repertoires across five species representing three mammalian lineages (marsupials, eutherians: rodents, primates) reveal that surprisingly few circRNAs arise from orthologous exonic loci across different species. Even the circRNAs from the orthologous loci are associated with young, recently active and species-specific transposable elements, rather than with common, ancient transposon integration events. These observations suggest that many circRNAs emerged convergently during evolution – as a byproduct of splicing in orthologs prone to transposable element insertion. Overall, our findings argue against widespread functional circRNA conservation.

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A Novel Intronic Circular RNA Antagonizes Influenza Virus by Absorbing a microRNA That Degrades CREBBP and Accelerating IFN-β Production

mBio ◽

10.1128/mbio.01017-21 ◽

2021 ◽

Author(s):

Zhiyuan Qu ◽

Fei Meng ◽

Jianzhong Shi ◽

Guohua Deng ◽

Xianying Zeng ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Circular Rna ◽

Human Diseases ◽

Circular Rnas ◽

New Members ◽

Multiple Functions ◽

Cellular Processes

Circular RNAs (circRNAs) are new members of the long noncoding RNA families and have been identified in a variety of organisms, including plants, animals, and humans. Accumulating data indicate that circRNAs perform multiple functions in a variety of cellular processes associated with human diseases, such as Alzheimer’s disease and cancer; however, the roles of circRNAs in virus infection have been largely uninvestigated.

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Systematic Identification and Analysis of Circular RNAs of Japanese Flounder (Paralichthys olivaceus) in Response to Vibrio anguillarum Infection

Genes ◽

10.3390/genes12010100 ◽

2021 ◽

Vol 12 (1) ◽

pp. 100

Author(s):

Xianhui Ning ◽

Li Sun

Keyword(s):

Paralichthys Olivaceus ◽

Expression Patterns ◽

Vibrio Anguillarum ◽

Circular Rna ◽

Japanese Flounder ◽

Immune Defense ◽

Circular Rnas ◽

Pathogen Infection ◽

North Asia ◽

Time Specific

Circular RNA (circRNA) is a new class of non-coding RNA that is structured into a closed loop without polyadenylation. Recent studies showed that circRNAs are involved in the host immune response to pathogen infection. Japanese flounder (Paralichthys olivaceus), an important economical marine fish cultured in north Asia, is affected by Vibrio anguillarum, a pathogenic bacterium that can infect a large number of fish. In this study, we systematically explored the circRNAs in the spleen of V. anguillarum-infected flounder at different infection time points. A total of 6581 circRNAs were identified, 148 of which showed differential expression patterns after V. anguillarum infection and were named DEcirs. Most of the DEcirs were strongly time-specific. The parental genes of the DEcirs were identified and functionally classified into diverse pathways, including immune-related pathways. Among the immune-related DEcirs, seven were predicted to sponge 18 targeted miRNAs that were differentially expressed during V. anguillarum infection (named DETmiRs). Further analysis showed that the DEcirs and their corresponding DETmiRs intertwined into complicated immune related networks. These results indicate that in flounder, circRNAs are regulated by V. anguillarum and form interactive networks with mRNAs and miRNAs that likely play important roles in the immune defense against pathogen infection.

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Circular and long non-coding RNAs and their role in ophthalmologic diseases

Acta Biochimica Polonica ◽

10.18388/abp.2018_2639 ◽

2018 ◽

Cited By ~ 5

Author(s):

Olga Wawrzyniak ◽

Żaneta Zarębska ◽

Katarzyna Rolle ◽

Anna Gotz-Więckowska

Keyword(s):

Current Knowledge ◽

Critical Role ◽

Circular Rna ◽

Age Related Macular Degeneration ◽

Circular Rnas ◽

Protein Coding ◽

Rna Molecules ◽

Age Related ◽

Non Coding Rnas ◽

Transcriptional Gene Regulation

Long non-coding RNAs are >200-nucleotide-long RNA molecules which lack or have limited protein-coding potential. They can regulate protein formation through several different mechanisms. Similarly, circular RNAs are reported to play a critical role in post-transcriptional gene regulation. Changes in the expression pattern of these molecules are known to underlie various diseases, including cancer, cardiovascular, neurological and immunological disorders (Rinn & Chang, 2012; Sun & Kraus, 2015). Recent studies suggest that they are differentially expressed both in healthy ocular tissues as well as in eye pathologies, such as neovascularization, proliferative vitreoretinopathy, glaucoma, cataract, ocular malignancy or even strabismus (Li et al., 2016). Aetiology of ocular diseases is multifactorial and combines genetic and environmental factors, including epigenetic and non-coding RNAs. In addition, disorders like diabetic retinopathy or age-related macular degeneration lack biomarkers for early detection as well as effective treatment methods that would allow controlling the disease progression at its early stages. The newly discovered non-coding RNAs seem to be the ideal candidates for novel molecular markers and therapeutic strategies. In this review, we summarized the current knowledge about gene expression regulators – long non-coding and circular RNA molecules in eye diseases.

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Targeting circular RNAs as a therapeutic approach: current strategies and challenges

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-021-00569-5 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Alina T. He ◽

Jinglei Liu ◽

Feiya Li ◽

Burton B. Yang

Keyword(s):

Therapeutic Approach ◽

High Specificity ◽

Circular Rna ◽

Circular Rnas ◽

Loss Of Function ◽

Cellular Processes ◽

Specific Manner ◽

Recent Developments ◽

A Cell ◽

Cell Type Specific

AbstractSignificant progress has been made in circular RNA (circRNA) research in recent years. Increasing evidence suggests that circRNAs play important roles in many cellular processes, and their dysregulation is implicated in the pathogenesis of various diseases. CircRNAs are highly stable and usually expressed in a tissue- or cell type-specific manner. Therefore, they are currently being explored as potential therapeutic targets. Gain-of-function and loss-of-function approaches are typically performed using circRNA expression plasmids and RNA interference-based strategies, respectively. These strategies have limitations that can be mitigated using nanoparticle and exosome delivery systems. Furthermore, recent developments show that the cre-lox system can be used to knockdown circRNAs in a cell-specific manner. While still in the early stages of development, the CRISPR/Cas13 system has shown promise in knocking down circRNAs with high specificity and efficiency. In this review, we describe circRNA properties and functions and highlight their significance in disease. We summarize strategies that can be used to overexpress or knockdown circRNAs as a therapeutic approach. Lastly, we discuss major challenges and propose future directions for the development of circRNA-based therapeutics.

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CircIMPACT: An R Package to Explore Circular RNA Impact on Gene Expression and Pathways

Genes ◽

10.3390/genes12071044 ◽

2021 ◽

Vol 12 (7) ◽

pp. 1044

Author(s):

Alessia Buratin ◽

Enrico Gaffo ◽

Anna Dal Molin ◽

Stefania Bortoluzzi

Keyword(s):

Gene Expression ◽

Rna Binding ◽

Rna Binding Proteins ◽

Experimental Studies ◽

R Package ◽

Circular Rna ◽

Circular Rnas ◽

Case Study Analysis ◽

Cellular Processes

Circular RNAs (circRNAs) are transcripts generated by back-splicing. CircRNAs might regulate cellular processes by different mechanisms, including interaction with miRNAs and RNA-binding proteins. CircRNAs are pleiotropic molecules whose dysregulation has been linked to human diseases and can drive cancer by impacting gene expression and signaling pathways. The detection of circRNAs aberrantly expressed in disease conditions calls for the investigation of their functions. Here, we propose CircIMPACT, a bioinformatics tool for the integrative analysis of circRNA and gene expression data to facilitate the identification and visualization of the genes whose expression varies according to circRNA expression changes. This tool can highlight regulatory axes potentially governed by circRNAs, which can be prioritized for further experimental study. The usefulness of CircIMPACT is exemplified by a case study analysis of bladder cancer RNA-seq data. The link between circHIPK3 and heparanase (HPSE) expression, due to the circHIPK3-miR558-HPSE regulatory axis previously determined by experimental studies on cell lines, was successfully detected. CircIMPACT is freely available at GitHub.

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CircSOD2: A Novel Regulator for Smooth Muscle Proliferation and Neointima Formation

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.121.316911 ◽

2021 ◽

Author(s):

Xiaohan Mei ◽

Xiao-Bing Cui ◽

Yiran Li ◽

Shi-You Chen

Keyword(s):

Smooth Muscle ◽

Vascular Injury ◽

Noncoding Rna ◽

Expression Patterns ◽

Ectopic Expression ◽

Circular Rna ◽

In Vivo Studies ◽

Circular Rnas ◽

Neointima Formation ◽

Specific Expression

Objective: Vascular smooth muscle cell (SMC) proliferation contributes to neointima formation following vascular injury. Circular RNA—a novel type of noncoding RNA with closed-loop structure—exhibits cell- and tissue-specific expression patterns. However, the role of circular RNA in SMC proliferation and neointima formation is largely unknown. The objective of this study is to investigate the role and mechanism of circSOD2 in SMC proliferation and neointima formation. Approach and Results: Circular RNA profiling of human aortic SMCs revealed that PDGF (platelet-derived growth factor)-BB up- and downregulated numerous circular RNAs. Among them, circSOD2, derived from back-splicing event of SOD2 (superoxide dismutase 2), was significantly enriched. Knockdown of circSOD2 by short hairpin RNA blocked PDGF-BB–induced SMC proliferation. Inversely, circSOD2 ectopic expression promoted SMC proliferation. Mechanistically, circSOD2 acted as a sponge for miR-206, leading to upregulation of NOTCH3 and NOTCH3 signaling, which regulates cyclin D1 and CDK (cyclin-dependent kinase) 4/6. In vivo studies showed that circSOD2 was induced in neointima SMCs in balloon-injured rat carotid arteries. Importantly, knockdown of circSOD2 attenuated injury-induced neointima formation along with decreased neointimal SMC proliferation. Conclusions: CircSOD2 is a novel regulator mediating SMC proliferation and neointima formation following vascular injury. Therefore, circSOD2 could be a potential therapeutic target for inhibiting the development of proliferative vascular diseases.

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