Identification of circular RNAs related to vascular endothelial proliferation, migration and angiogenesis after spinal cord injury using microarray analysis
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE166967 | GEO | 2021/08/30
REPOSITORIES: GEO
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Project description:Circular RNAs (circRNAs) are a large class of animal RNAs. To investigate possible circRNA functions, it is important to understand circRNA biogenesis. Besides human Alu repeats, sequence features that promote exon circularization are largely unknown. We experimentally identified new circRNAs in C. elegans. Reverse complementary sequences between introns bracketing circRNAs were significantly enriched compared to linear controls. By scoring the presence of reverse complementary sequences in human introns we predicted and experimentally validated novel circRNAs. We show that introns bracketing circRNAs are highly enriched in RNA editing or hyper-editing events. Knockdown of the double-strand RNA editing ADAR1 enzyme significantly and specifically up-regulated circRNA expression. Together, our data support a model of animal circRNA biogenesis in which competing RNA:RNA interactions of introns form larger structures which promote circularization of embedded exons, while ADAR1 antagonizes circRNA expression by melting stems within these interactions. Thus, we assign a new function to ADAR1. Examination of 12 samples in different stages of C.elegans development.
2015-01-06 | E-GEOD-63823 | biostudies-arrayexpress
Project description:Injured axons in the CNS do not spontaneously regenerate leading to paralysis. Neurons can transport RNA and ribosomes to the site of injury where de novo translation has been known to occur, facilitating repair. Yet the tools available for studying axonal specific RNA are limited. We came up with a simple modification using Cold Active Proteases that enabled us to enrich for axonal RNA from rats with spinal cord injury (SCI) compared to non-injured. Our enriched axonal prep was then analyzed by bulk RNA-seq, where we looked at total RNA and we found differentially expressed genes (DEGs). Analyzing our bulk RNA-seq by Gene Ontology, we found the second most significant pathway for all DEGs was for axonogenesis, with markedly low glial cell contamination. From our DEGs we detected Rims2, which is reported to be predominately a circular RNA (circRNA) in the rodent CNS. Upon further annotation, we found over 200 putative circRNAs. circRNAs are abundant and well conserved in the brain, they are thought to be transcriptional regulators by functioning as microRNA (miR) sponges or binding to RNA-binding proteins (RBPs). By computational analysis using Circular RNA Interactome, we are able to predict which miRs or RBPs could bind to circRims2.
2023-07-25 | GSE230066 | GEO
Project description:Circular RNAs (circRNAs) are an endogenous class of animal RNAs. Despite their abundance, their function and expression in the nervous system are unknown. Therefore, we sequenced RNA from different brain regions, primary neurons, isolated synapses, as well as during neuronal differentiation. Using these and other available data, we discovered and analyzed thousands of neuronal human and mouse circRNAs. circRNAs were extraordinarily enriched in the mammalian brain, well conserved in sequence, often expressed as circRNAs in both human and mouse, and sometimes even detected in Drosophila brains. circRNAs were overall upregulated during neuronal differentiation, highly enriched in synapses, and often differentially expressed compared to their mRNA isoforms. circRNA expression correlated negatively with expression of the RNA-editing enzyme ADAR1. Knockdown of ADAR1 induced elevated circRNA expression. Together, we provide a circRNA brain expression atlas and evidence for important circRNA functions and values as biomarkers. To assess circRNA expression in mammalian brain, we sequenced and analyzed mouse brain regions (hippocampus, cerebellum, prefrontal cortex and olfactory bulb), various neuronal differentiation (mouse P19 and human SH-SY5Y cells) and maturation (mouse cortical neurons) stages, and subcellular compartments in mouse (synaptoneurosomal fraction, cytoplasmic fraction, whole brain lysate).
2015-04-24 | E-GEOD-65926 | biostudies-arrayexpress
Project description:Background: Traumatic spinal cord injury (SCI) can result in severe disability and causes a considerable socio-economic burden worldwide. Circular RNAs (circRNAs) are important regulators of gene expression and pathological processes, and may represent therapeutic targets for SCI. To further evaluate the role of circRNAs in SCI, we elucidated circRNA expression profiles related to vascular endothelial proliferation, migration, and angiogenesis during the early stages of secondary injury in a mouse model of SCI. Methods: Microarray analysis was performed to investigate the circRNA expression patterns in the spinal cord 3 days after SCI in female mice. Bioinformatic analyses, including GO enrichment analysis, KEGG pathway analysis, and circRNA-miRNA-mRNA network construction, were conducted to explore the role of circRNA dysregulation in vascular endothelial proliferation, migration, and angiogenesis following SCI. Results: The expression of 1,288 circRNAs was altered (>2-fold change, p < 0.05) in the spinal cord after SCI, consisting of 991 upregulated and 297 downregulated circRNAs. We constructed a circRNA-mRNA network to predict whether these circRNAs could act as "miRNA sponges." We next assessed the association of altered circRNAs with vascular endothelial proliferation, migration, and angiogenesis using GO and KEGG analyses. Using this analysis, we found that a total of 121 circRNAs were correlated with vascular endothelial proliferation, migration, and angiogenesis in the spinal cord after SCI. Conclusions: Our study provides circRNA expression profiles during the early stages of SCI. circRNA.7079, circRNA.7078, and circRNA.6777 were found to play key roles in the vascular endothelial proliferation, migration, and angiogenesis, and may represent therapeutic targets for SCI.
| S-EPMC8447959 | biostudies-literature
Project description:The human genome encodes tens of thousands circular RNAs (circRNAs) whose levels correlate with many disease states. While studies have focused on the non-coding functions of circRNAs, emerging evidence suggests that a handful of circRNAs encode proteins. Translation canonically starts by recognition of mRNA 5’cap and scanning to the start codon; how circRNA translation initiates remains unclear. Here, we developed a high-throughput screen to systematically identify and quantify RNA sequences that can direct circRNA translation. We identify and validate over 17,000 circRNA internal ribosome entry sites (IRES) and reveal that 18S rRNA complementarity and a structured RNA element on the IRES are important for facilitating circRNA cap-independent translation. With genomic and peptidomic analyses of the IRES, we identified nearly 1,000 putative endogenous protein-coding circRNAs and hundreds of translational units encoded by these circRNAs. We further characterized circFGFR1p, a protein encoded by circFGFR1, functions as a negative regulator of FGFR1 to suppress cell growth under stress conditions. The circRNA proteome may be important links among circRNA, biological control, and disease.
2021-08-25 | PXD025233 | Pride
Project description:The human genome encodes tens of thousands circular RNAs (circRNAs) whose levels correlate with many disease states. While studies have focused on the non-coding functions of circRNAs, emerging evidence suggests that a handful of circRNAs encode proteins. Translation canonically starts by recognition of mRNA 5’cap and scanning to the start codon; how circRNA translation initiates remains unclear. Here, we developed a high-throughput screen to systematically identify and quantify RNA sequences that can direct circRNA translation. We identify and validate over 17,000 circRNA internal ribosome entry sites (IRES) and reveal that 18S rRNA complementarity and a structured RNA element on the IRES are important for facilitating circRNA cap-independent translation. With genomic and peptidomic analyses of the IRES, we identified nearly 1,000 putative endogenous protein-coding circRNAs and hundreds of translational units encoded by these circRNAs. We further characterized circFGFR1p, a protein encoded by circFGFR1, functions as a negative regulator of FGFR1 to suppress cell growth under stress conditions. The circRNA proteome may be important links among circRNA, biological control, and disease.
2021-08-26 | PXD025203 | Pride
Project description:The human genome encodes tens of thousands circular RNAs (circRNAs) whose levels correlate with many disease states. While studies have focused on the non-coding functions of circRNAs, emerging evidence suggests that a handful of circRNAs encode proteins. Translation canonically starts by recognition of mRNA 5’cap and scanning to the start codon; how circRNA translation initiates remains unclear. Here, we developed a high-throughput screen to systematically identify and quantify RNA sequences that can direct circRNA translation. We identify and validate over 17,000 circRNA internal ribosome entry sites (IRES) and reveal that 18S rRNA complementarity and a structured RNA element on the IRES are important for facilitating circRNA cap-independent translation. With genomic and peptidomic analyses of the IRES, we identified nearly 1,000 putative endogenous protein-coding circRNAs and hundreds of translational units encoded by these circRNAs. We further characterized circFGFR1p, a protein encoded by circFGFR1, functions as a negative regulator of FGFR1 to suppress cell growth under stress conditions. The circRNA proteome may be important links among circRNA, biological control, and disease.
2021-08-23 | PXD024993 | Pride
Project description:The human genome encodes tens of thousands circular RNAs (circRNAs) whose levels correlate with many disease states. While studies have focused on the non-coding functions of circRNAs, emerging evidence suggests that a handful of circRNAs encode proteins. Translation canonically starts by recognition of mRNA 5’cap and scanning to the start codon; how circRNA translation initiates remains unclear. Here, we developed a high-throughput screen to systematically identify and quantify RNA sequences that can direct circRNA translation. We identify and validate over 17,000 circRNA internal ribosome entry sites (IRES) and reveal that 18S rRNA complementarity and a structured RNA element on the IRES are important for facilitating circRNA cap-independent translation. With genomic and peptidomic analyses of the IRES, we identified nearly 1,000 putative endogenous protein-coding circRNAs and hundreds of translational units encoded by these circRNAs. We further characterized circFGFR1p, a protein encoded by circFGFR1, functions as a negative regulator of FGFR1 to suppress cell growth under stress conditions. The circRNA proteome may be important links among circRNA, biological control, and disease.
2021-08-23 | PXD025235 | Pride
Project description:Circular RNA is implicated in numerous diseases and conditions, including traumatic injury to the central nervoussystem. However, we know little regarding their role in completely transected spinal cord injury (SCI). Our studyused high-throughput sequencing to analyze circular RNA expression in rats after experimental completetransection of spinal cord. We found differential expression in 400 circular RNAs after SCI, with 249 significantlyup-regulated and 151 significantly down-regulated. We then selected five circular RNAs for qRT-PCR validation,and the results were in agreement with RNA sequencing. Additionally, we predicted the function of circular RNAin SCI through GO and KEGG analyses, as well as the construction of circRNA/microRNA interaction networks.Furthermore, we identified circular RNA chr9:1829226-1834212 and mRNA Hdac11 as key molecules after SCI.In conclusion, this study is the first to characterize circular RNA function in rats after completely transected SCI,through identifying their differential expression. Our results provide insight into the mechanism and therapeutictargets of SCI.
2020-08-28 | GSE156999 | GEO
Project description:Circular RNAs (circRNAs) exhibit diverse intracellular functions through their ability to bind to RNA, DNA, and protein structures, influencing biological processes at both transcriptional and post-transcriptional levels. To date, however, few studies have sought to profile circRNA expression in the epicentral regions of spinal lesions in the context of spinal cord injury (SCI). Accordingly, this study was designed to assess circRNA and mRNA expression profiles in this pathological setting so as to gain insight regarding the ability of circRNAs to influence SCI development and resolution. A microarray-based approach was thus used to simultaneously measure the levels of these RNAs, with qPCR, fluorescence in situ hybridization and Western immunoblotting being further used to expand on these analyses and associated regulatory mechanisms in a rat SCI model system. In total, SCI was found to be associated with the differential expression of 414 and 5337 circRNAs and mRNAs, respectively. Pathway enrichment analyses suggested that these abnormally expressed circRNAs and mRNAs were associated with key SCI-related pathways and processes, with the cytokine-cytokine receptor interaction and neuroactive ligand-receptor interaction pathways being most strongly enriched. GSEA analyses of all identified mRNAs revealed that those which were differentially expressed were primarily associated with inflammatory immune response activity. Further screening of these inflammation-associated genes was used to construct and analyze a competing endogenous RNA network. Overall, these results emphasize the critical roles that circRNAs are likely to play in the pathophysiology of SCI, highlighting multiple important genes that play regulatory roles in this setting and providing a robust foundation for further research exploring the mechanisms governing the pathogenesis and potential therapeutic targets of SCI.
2022-08-06 | GSE210609 | GEO