scholarly journals Circular RNA repertoires are associated with evolutionarily young transposable elements

eLife ◽  
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.

scholarly journals Circular RNA repertoires are associated with evolutionarily young transposable elements

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.

Miniature inverted repeat transposable elements (MITEs) cis-regulate circular RNA expression and promote ethylene biosynthesis, reducing poplar heat tolerance

2020 ◽  
Author(s):  
Yuepeng Song ◽  
Chenhao Bu ◽  
Panfei Chen ◽  
Peng Liu ◽  
Deqiang Zhang
Keyword(s):  
Transposable Elements ◽  
Heat Tolerance ◽  
Protein Modification ◽  
Membrane Lipids ◽  
Circular Rna ◽  
Ethylene Biosynthesis ◽  
Negative Regulator ◽  
Circular Rnas ◽  
Nucleotide Polymorphisms ◽  
Complementary Sequence

Abstract Transposable elements (TEs) and their reverse complementary sequence pairs (RCPs) are enriched around loci that produce circular RNAs (circRNAs) in plants. However, the function of these TE–RCP pairs in modulating circRNA expression remains elusive. Here, we identified 4,609 circRNAs in poplar (Populus tomentosa) and showed that MITEs-RCPs were enriched in circRNA flanking regions. Moreover, we used expression quantitative trait nucleotide (eQTN) mapping to decipher the cis-regulatory role of MITEs. eQTN results showed that fourteen single-nucleotide polymorphisms (SNPs) were significantly associated with Circ_0000408 and Circ_0003418 levels and the lead associated SNPs were located in MITE–RCP regions, indicating that MITE-RCP sequence variations affect exon circularization. Overexpression and knockdown analysis showed that Circ_0003418 positively modulated its parental gene, which encodes the RING-type E3 ligase XBAT32, and specifically increased the expression of the PtoXBAT32.5 transcript variant, which lacks the E3 ubiquitin ligase domain. Under heat stress, PtoXBAT32.5 expression was induced with upregulation of Circ_0003418, resulting in increased production of ethylene and peroxidation of membrane lipids. Our findings thus reveal the cis-regulatory mechanism by which a MITE–RCP pair affects circRNA abundance in poplar and indicate that Circ_0003418 is a negative regulator of poplar heat tolerance via the ubiquitin-mediated protein modification pathway.

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

2018 ◽  
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.

scholarly journals Centromere Repeats: Hidden Gems of the Genome

Genes ◽  
2019 ◽  
Vol 10 (3) ◽  
pp. 223 ◽  
Author(s):  
Gabrielle Hartley ◽  
Rachel O’Neill
Keyword(s):  
Transposable Elements ◽  
De Novo ◽  
Chromosomal Rearrangements ◽  
Repetitive Sequences ◽  
Chromosomal Evolution ◽  
Satellite Dnas ◽  
Integral Role ◽  
Chromosomal Breakpoints ◽  
Karyotypic Variation ◽  
Species Specific

Satellite DNAs are now regarded as powerful and active contributors to genomic and chromosomal evolution. Paired with mobile transposable elements, these repetitive sequences provide a dynamic mechanism through which novel karyotypic modifications and chromosomal rearrangements may occur. In this review, we discuss the regulatory activity of satellite DNA and their neighboring transposable elements in a chromosomal context with a particular emphasis on the integral role of both in centromere function. In addition, we discuss the varied mechanisms by which centromeric repeats have endured evolutionary processes, producing a novel, species-specific centromeric landscape despite sharing a ubiquitously conserved function. Finally, we highlight the role these repetitive elements play in the establishment and functionality of de novo centromeres and chromosomal breakpoints that underpin karyotypic variation. By emphasizing these unique activities of satellite DNAs and transposable elements, we hope to disparage the conventional exemplification of repetitive DNA in the historically-associated context of ‘junk’.

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

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Yılmaz Mehmet Demirci ◽  
Müşerref Duygu Saçar Demirci
Keyword(s):  
Graphical Representation ◽  
Expression Patterns ◽  
Circular Rna ◽  
Circular Rnas ◽  
Viral Mrnas ◽  
Cellular Processes ◽  
Human Mirnas ◽  
Different Types ◽  
Analysis Workflow ◽  
Transcriptional Gene Regulation

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.

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.

scholarly journals The circular RNA circSlc7a11 promotes bone cancer pain pathogenesis in rats by modulating LLC-WRC 256 cell proliferation and apoptosis

2021 ◽  
Author(s):  
Han-Wen Chen ◽  
Xiao-Xia Zhang ◽  
Zhu-Ding Peng ◽  
Zu-Min Xing ◽  
Yi-Wen Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cancer Pain ◽  
Expression Profiles ◽  
Bone Cancer ◽  
Circular Rna ◽  
Differentially Expressed ◽  
Bone Cancer Pain ◽  
Circular Rnas ◽  
Altered Expression ◽  
Proliferation And Apoptosis

AbstractTreatment of bone cancer pain (BCP) caused by bone metastasis in advanced cancers remains a challenge in clinical oncology, and the underlying mechanisms of BCP are poorly understood. This study aimed to investigate the pathogenic roles of circular RNAs (circRNAs) in regulating cancer cell proliferation and BCP development. Eight differentially expressed circRNAs in the rat spinal cord were validated by agarose gel electrophoresis and Sanger sequencing. Expression of circRNAs and mRNAs was detected by quantitative RT-PCR. MTS assay and flow cytometry were performed to analyze cell proliferation and apoptosis, respectively. Differentially expressed mRNA profiles were characterized by deep RNA sequencing, hierarchical clustering, and functional categorization. The interactions among circRNAs, microRNAs (miRNAs), and mRNAs were predicted using TargetScan. Additionally, western blot was performed to determine the protein levels of Pax8, Isg15, and Cxcl10. Multiple circRNAs were differentially expressed in the spinal cords of BCP model rats; of these, circSlc7a11 showed the greatest increase in expression. The overexpression of circSlc7a11 significantly promoted cell proliferation and repressed apoptosis of LLC-WRC 256 and UMR-106 cells, whereas circSlc7a11 silencing produced the opposite effects. Altered expression of circSlc7a11 also induced substantial changes in the mRNA expression profiles of LLC-WRC 256 cells; these changes were linked to multiple apoptotic processes and signaling pathways, such as the chemokine signaling pathway, and formed a complex circRNA/miRNA/mRNA network. Additionally, Pax8, Isg15, and Cxc110 protein level in LLC-WRC 256 cells was consistent with the mRNA results. The circRNA circSlc7a11 regulates rat BCP development by modulating LLC-WRC 256 cell proliferation and apoptosis through multiple-signaling mechanisms.

scholarly journals Correlation of Circular RNA hsa_circ_0001946, hsa_circ_0125589, and Environmental Factors With Hypertension

2020 ◽  
Vol 33 (11) ◽  
pp. 1047-1047
Author(s):  
Wan-yue Liu ◽  
Yi Sun ◽  
Shu-na Huang ◽  
Yu-zhen Lin ◽  
Hong-yan Guo ◽  
...  
Keyword(s):  
Environmental Factors ◽  
Peripheral Blood ◽  
Circular Rna ◽  
Peripheral Blood Lymphocytes ◽  
Normal Weight ◽  
Circular Rnas ◽  
Blood Leukocytes ◽  
Crossover Analysis ◽  
History Of ◽  
The Relationship

Abstract Background To investigate the main environmental factors of hypertension and the relationship between hypertension and circular RNAs in peripheral blood lymphocytes. Methods This was a case–control study. A total of 681 hypertension patients and 485 subjects without hypertension were recruited between April 2017 and October 2018. All participations completed the questionnaire investigation, physical examination, and laboratory detection. Quantitative real-time polymerase chain reaction was used to analyze circRNAs (hsa_circ_0001946 and hsa_circ_0125589) in peripheral blood leukocytes in 84 hypertensives and 84 controls. Multivariate logistic regression and crossover analysis were used to analyze the interaction and association between environmental factors and circRNAs in hypertension. Results After adjusted by gender, age and marital status, overweight/obesity (odds ratio (OR) = 1.66, 95% confidence interval (CI) 1.24–2.22), abdominal obesity (OR = 2.17, 95% CI 1.54–3.04), anxiety (OR = 2.15, 95% CI 1.41–3.28), family history of hypertension (OR = 4.26, 95% CI 3.18–5.70), and higher levels of hsa_circ_0001946 (OR = 4.13, 95% CI 1.85–9.21) were risk factors for hypertension, while levels of hsa_circ_0125589 were not associated with hypertension. Crossover analysis showed that the risk of hypertension was 13.12 times higher (95% CI 3.89–44.23) in overweight subjects with high hsa_circ_0001946 levels compared with normal weight subjects with low hsa_circ_0001946 levels. Further, the risk of hypertension was 17.78 times higher (95% CI 1.88–168.61) in subjects with anxiety and high hsa_circ_0001946 levels. Conclusions Hypertension is the result of both environmental factors and genetic factors. Higher hsa_circ_0001946 levels, overweight and anxiety may increase the risk of hypertension, while hsa_circ_0125589 levels are not related to hypertension.

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