scholarly journals Identification of Potential circRNA-microRNA-mRNA Regulatory Network in Skeletal Muscle

2021 ◽  
Vol 8 ◽  
Author(s):  
Arundhati Das ◽  
Sharmishtha Shyamal ◽  
Tanvi Sinha ◽  
Smruti Sambhav Mishra ◽  
Amaresh C. Panda
Keyword(s):  
Skeletal Muscle ◽  
Regulatory Network ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Circular Rnas ◽  
Regulate Gene Expression ◽  
Mouse Skeletal Muscle ◽  
Muscle Tissues ◽  
Genome Wide ◽  
Regulatory Rnas

Circular RNAs (circRNAs) are a newly discovered family of regulatory RNAs generated through backsplicing. Genome-wide profiling of circRNAs found that circRNAs are ubiquitously expressed and regulate gene expression by acting as a sponge for RNA-binding proteins (RBPs) and microRNAs (miRNAs). To identify circRNAs expressed in mouse skeletal muscle, we performed high-throughput RNA-sequencing of circRNA-enriched gastrocnemius muscle RNA samples, which identified more than 1,200 circRNAs. In addition, we have identified more than 14,000 and 15,000 circRNAs in aging human skeletal muscle tissue and satellite cells, respectively. A subset of abundant circRNAs was analyzed by RT-PCR, Sanger sequencing, and RNase R digestion assays to validate their expression in mouse skeletal muscle tissues. Analysis of the circRNA-miRNA-mRNA regulatory network revealed that conserved circNfix might associate with miR-204-5p, a suppressor of myocyte enhancer factor 2c (Mef2c) expression. To support the hypothesis that circNfix might regulate myogenesis by controlling Mef2c expression, silencing circNfix moderately reduced Mef2c mRNA expression and inhibited C2C12 differentiation. We propose that circNfix promotes MEF2C expression during muscle cell differentiation in part by acting as a sponge for miR-204-5p.

scholarly journals Large-Scale Profiling of RBP-circRNA Interactions from Public CLIP-Seq Datasets

2019 ◽  
Author(s):  
Minzhe Zhang ◽  
Tao Wang ◽  
Guanghua Xiao ◽  
Yang Xie
Keyword(s):  
Large Scale ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Read Length ◽  
Circular Rnas ◽  
Binding Partners ◽  
Genome Wide ◽  
Wide Scale ◽  
And Function ◽  
Short Read Length

Circular RNAs are a special type of RNAs which recently attracted a lot of research interest in studying its formation and function. RNA binding proteins (RBPs) that bind circRNAs are important in these processes but are relatively less studied. CLIP-Seq technology has been invented and applied to profile RBP-RNA interactions on the genome-wide scale. While mRNAs are usually the focus of CLIP-Seq experiments, RBP-circRNA interactions could also be identified through specialized analysis of CLIP-Seq datasets. However, many technical difficulties are involved in this process, such as the usually short read length of CLIP-Seq reads. In this study, we created a pipeline called Clirc specialized for profiling circRNAs in CLIP-Seq data and analyzing the characteristics of RBP- circRNAs interactions. In conclusion, this is one of the first few studies to investigate circRNAs and their binding partners through repurposing CLIP-Seq datasets to our knowledge, and we hope our work will become a valuable resource for future studies into the biogenesis and function of circRNAs. Clirc software is available at https://github.com/Minzhe/Clirc

scholarly journals circVAR database: genome-wide archive of genetic variants for human circular RNAs

2020 ◽  
Author(s):  
Min Zhao ◽  
Hong Qu
Keyword(s):  
Genetic Variants ◽  
Complex Traits ◽  
Large Scale ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Association Studies ◽  
Chromosome 17 ◽  
Circular Rnas ◽  
Genome Wide Association Studies ◽  
Genome Wide

Abstract Background: Circular RNAs (circRNAs) play important roles in regulating gene expression through binding miRNAs and RNA binding proteins. Genetic variation of circRNAs may affect complex traits/diseases by changing their binding efficiency to target miRNAs and proteins. There is a growing demand for investigations of the functions of genetic changes using large-scale experimental evidence. However, there is no online genetic resource for circRNA genes. Results: We performed extensive genetic annotation of 295,526 circRNAs integrated from circBase, circNet and circRNAdb. All pre-computed genetic variants were presented at our online resource, circVAR, with data browsing and search functionality. We explored the chromosome-based distribution of circRNAs and their associated variants. We found that, based on mapping to the 1000 Genomes and ClinVAR databases, chromosome 17 has a relatively large number of circRNAs and associated common and health-related genetic variants. Following the annotation of genome wide association studies (GWAS)-based circRNA variants, we found many non-coding variants within circRNAs, suggesting novel mechanisms for common diseases reported from GWAS studies. For cancer-based somatic variants, we found that chromosome 7 has many highly complex mutations that have been overlooked in previous research. Conclusion: We used the circVAR database to collect SNPs and small insertions and deletions (INDELs) in putative circRNA regions and to identify their potential phenotypic information. To provide a reusable resource for the circRNA research community, we have published all the pre-computed genetic data concerning circRNAs and associated genes together with data query and browsing functions at http://soft.bioinfo-minzhao.org/circvar .

scholarly journals circVAR Database: Genome-Wide Archive of Genetic Variants for Human Circular RNAs

2020 ◽  
Author(s):  
Min Zhao ◽  
Hong Qu
Keyword(s):  
Genetic Variants ◽  
Complex Traits ◽  
Large Scale ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Association Studies ◽  
Chromosome 17 ◽  
Circular Rnas ◽  
Genome Wide Association Studies ◽  
Genome Wide

Abstract Background: Circular RNAs (circRNAs) play important roles in regulating gene expression through binding miRNAs and RNA binding proteins. Genetic variation of circRNAs may affect complex traits/diseases by changing their binding efficiency to target miRNAs and proteins. There is a growing demand for investigations of the functions of genetic changes using large-scale experimental evidence. However, there is no online genetic resource for circRNA genes. Results: We performed extensive genetic annotation of 295,526 circRNAs integrated from circBase, circNet and circRNAdb. All pre-computed genetic variants were presented at our online resource, circVAR, with data browsing and search functionality. We explored the chromosome-based distribution of circRNAs and their associated variants. We found that, based on mapping to the 1000 Genomes and ClinVAR databases, chromosome 17 has a relatively large number of circRNAs and associated common and health-related genetic variants. Following the annotation of genome wide association studies (GWAS)-based circRNA variants, we found many non-coding variants within circRNAs, suggesting novel mechanisms for common diseases reported from GWAS studies. For cancer-based somatic variants, we found that chromosome 7 has many highly complex mutations that have been overlooked in previous research.Conclusion: We used the circVAR database to collect SNPs and small insertions and deletions (INDELs) in putative circRNA regions and to identify their potential phenotypic information. To provide a reusable resource for the circRNA research community, we have published all the pre-computed genetic data concerning circRNAs and associated genes together with data query and browsing functions at http://soft.bioinfo-minzhao.org/circvar.

scholarly journals Large-Scale Profiling of RBP-circRNA Interactions from Public CLIP-Seq Datasets

Genes ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 54 ◽  
Author(s):  
Minzhe Zhang ◽  
Tao Wang ◽  
Guanghua Xiao ◽  
Yang Xie
Keyword(s):  
Large Scale ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Read Length ◽  
Circular Rnas ◽  
Binding Partners ◽  
Genome Wide ◽  
Wide Scale ◽  
And Function ◽  
Short Read Length

Circular RNAs are a special type of RNA that has recently attracted a lot of research interest in studying its formation and function. RNA binding proteins (RBPs) that bind circRNAs are important in these processes, but have been relatively less studied. CLIP-Seq technology has been invented and applied to profile RBP-RNA interactions on the genome-wide scale. While mRNAs are usually the focus of CLIP-Seq experiments, RBP-circRNA interactions could also be identified through specialized analysis of CLIP-Seq datasets. However, many technical difficulties are involved in this process, such as the usually short read length of CLIP-Seq reads. In this study, we created a pipeline called Clirc specialized for profiling circRNAs in CLIP-Seq data and analyzing the characteristics of RBP-circRNA interactions. In conclusion, to our knowledge, this is one of the first studies to investigate circRNAs and their binding partners through repurposing CLIP-Seq datasets, and we hope our work will become a valuable resource for future studies into the biogenesis and function of circRNAs.

scholarly journals circVAR database: genome-wide archive of genetic variants for human circular RNAs

BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Min Zhao ◽  
Hong Qu
Keyword(s):  
Genetic Variants ◽  
Complex Traits ◽  
Large Scale ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Association Studies ◽  
Chromosome 17 ◽  
Circular Rnas ◽  
Genome Wide Association Studies ◽  
Genome Wide

Abstract Background Circular RNAs (circRNAs) play important roles in regulating gene expression through binding miRNAs and RNA binding proteins. Genetic variation of circRNAs may affect complex traits/diseases by changing their binding efficiency to target miRNAs and proteins. There is a growing demand for investigations of the functions of genetic changes using large-scale experimental evidence. However, there is no online genetic resource for circRNA genes. Results We performed extensive genetic annotation of 295,526 circRNAs integrated from circBase, circNet and circRNAdb. All pre-computed genetic variants were presented at our online resource, circVAR, with data browsing and search functionality. We explored the chromosome-based distribution of circRNAs and their associated variants. We found that, based on mapping to the 1000 Genomes and ClinVAR databases, chromosome 17 has a relatively large number of circRNAs and associated common and health-related genetic variants. Following the annotation of genome wide association studies (GWAS)-based circRNA variants, we found many non-coding variants within circRNAs, suggesting novel mechanisms for common diseases reported from GWAS studies. For cancer-based somatic variants, we found that chromosome 7 has many highly complex mutations that have been overlooked in previous research. Conclusion We used the circVAR database to collect SNPs and small insertions and deletions (INDELs) in putative circRNA regions and to identify their potential phenotypic information. To provide a reusable resource for the circRNA research community, we have published all the pre-computed genetic data concerning circRNAs and associated genes together with data query and browsing functions at http://soft.bioinfo-minzhao.org/circvar.

scholarly journals Genome-wide bioinformatic analyses predict key host and viral factors in SARS-CoV-2 pathogenesis

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Mariana G. Ferrarini ◽  
Avantika Lal ◽  
Rita Rebollo ◽  
Andreas J. Gruber ◽  
Andrea Guarracino ◽  
...  
Keyword(s):  
Transposable Element ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Initiation Factor ◽  
Sequence Variant ◽  
The Novel ◽  
Sequencing Data ◽  
Genome Wide ◽  
Respiratory Cells ◽  
Nuclear Ribonucleoprotein

AbstractThe novel betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a worldwide pandemic (COVID-19) after emerging in Wuhan, China. Here we analyzed public host and viral RNA sequencing data to better understand how SARS-CoV-2 interacts with human respiratory cells. We identified genes, isoforms and transposable element families that are specifically altered in SARS-CoV-2-infected respiratory cells. Well-known immunoregulatory genes including CSF2, IL32, IL-6 and SERPINA3 were differentially expressed, while immunoregulatory transposable element families were upregulated. We predicted conserved interactions between the SARS-CoV-2 genome and human RNA-binding proteins such as the heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) and eukaryotic initiation factor 4 (eIF4b). We also identified a viral sequence variant with a statistically significant skew associated with age of infection, that may contribute to intracellular host–pathogen interactions. These findings can help identify host mechanisms that can be targeted by prophylactics and/or therapeutics to reduce the severity of COVID-19.

scholarly journals Identification of Novel RNA Binding Proteins Influencing Circular RNA Expression in Hepatocellular Carcinoma

2021 ◽  
Vol 22 (14) ◽  
pp. 7477
Author(s):  
Rok Razpotnik ◽  
Petra Nassib ◽  
Tanja Kunej ◽  
Damjana Rozman ◽  
Tadeja Režen
Keyword(s):  
Hepatocellular Carcinoma ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Regulatory Protein ◽  
Circular Rna ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Bioinformatics Analyses ◽  
Published Evidence

Circular RNAs (circRNAs) are increasingly recognized as having a role in cancer development. Their expression is modified in numerous cancers, including hepatocellular carcinoma (HCC); however, little is known about the mechanisms of their regulation. The aim of this study was to identify regulators of circRNAome expression in HCC. Using publicly available datasets, we identified RNA binding proteins (RBPs) with enriched motifs around the splice sites of differentially expressed circRNAs in HCC. We confirmed the binding of some of the candidate RBPs using ChIP-seq and eCLIP datasets in the ENCODE database. Several of the identified RBPs were found to be differentially expressed in HCC and/or correlated with the overall survival of HCC patients. According to our bioinformatics analyses and published evidence, we propose that NONO, PCPB2, PCPB1, ESRP2, and HNRNPK are candidate regulators of circRNA expression in HCC. We confirmed that the knocking down the epithelial splicing regulatory protein 2 (ESRP2), known to be involved in the maintenance of the adult liver phenotype, significantly changed the expression of candidate circRNAs in a model HCC cell line. By understanding the systemic changes in transcriptome splicing, we can identify new proteins involved in the molecular pathways leading to HCC development and progression.

scholarly journals Comprehensive landscape and future perspectives of circular RNAs in colorectal cancer

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Fei Long ◽  
Zhi Lin ◽  
Liang Li ◽  
Min Ma ◽  
Zhixing Lu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Circular Rnas ◽  
Future Perspectives ◽  
Cis Acting ◽  
New Class ◽  
Functional Peptides ◽  
Mirna Sponges

AbstractColorectal cancer (CRC) is a common hereditary tumor that is often fatal. Its pathogenesis involves multiple genes, including circular RNAs (circRNAs). Notably, circRNAs constitute a new class of noncoding RNAs (ncRNAs) with a covalently closed loop structure and have been characterized as stable, conserved molecules that are abundantly expressed in tissue/development-specific patterns in eukaryotes. Based on accumulating evidence, circRNAs are aberrantly expressed in CRC tissues, cells, exosomes, and blood from patients with CRC. Moreover, numerous circRNAs have been identified as either oncogenes or tumor suppressors that mediate tumorigenesis, metastasis and chemoradiation resistance in CRC. Although the regulatory mechanisms of circRNA biogenesis and functions remain fairly elusive, interesting results have been obtained in studies investigating CRC. In particular, the expression of circRNAs in CRC is comprehensively modulated by multiple factors, such as splicing factors, transcription factors, specific enzymes and cis-acting elements. More importantly, circRNAs exert pivotal effects on CRC through various mechanisms, including acting as miRNA sponges or decoys, interacting with RNA binding proteins, and even translating functional peptides. Finally, circRNAs may serve as promising diagnostic and prognostic biomarkers and potential therapeutic targets in the clinical practice of CRC. In this review, we discuss the dysregulation, functions and clinical significance of circRNAs in CRC and further discuss the molecular mechanisms by which circRNAs exert their functions and how their expression is regulated. Based on this review, we hope to reveal the functions of circRNAs in the initiation and progression of cancer and highlight the future perspectives on strategies targeting circRNAs in cancer research.

scholarly journals Genome-wide Identification and Expression Analysis of the YTH Domain-containing RNA-binding Protein Family in Citrus Sinensis

2019 ◽  
Vol 144 (2) ◽  
pp. 79-91 ◽  
Author(s):  
Zhigang Ouyang ◽  
Huihui Duan ◽  
Lanfang Mi ◽  
Wei Hu ◽  
Jianmei Chen ◽  
...  
Keyword(s):  
Stress Responses ◽  
Messenger Rna ◽  
Citrus Sinensis ◽  
Rna Binding ◽  
Developmental Stages ◽  
Rna Binding Proteins ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Genome Wide ◽  
Yth Domain

In eukaryotic systems, messenger RNA regulations, including splicing, 3′-end formation, editing, localization, and translation, are achieved by different RNA-binding proteins and noncoding RNAs. The YTH domain is a newly identified RNA-binding domain that was identified by comparing its sequence with that of splicing factor YT521-B. Previous study showed that the YTH gene plays an important role in plant resistance to abiotic and biotic stress. In this study, 211 YTH genes were identified in 26 species that represent four major plant lineages. Phylogenetic analysis revealed that these genes could be divided into eight subgroups. All of the YTH genes contain a YT521 domain and have different structures. Ten YTH genes were identified in navel orange (Citrus sinensis). The expression profiles of these CitYTH genes were analyzed in different tissues and at different fruit developmental stages, and CitYTH genes displayed distinct expression patterns under heat, cold, salt, and drought stress. Furthermore, expression of the CitYTH genes in response to exogenous hormones was measured. Nuclear localization was also confirmed for five of the proteins encoded by these genes after transient expression in Nicotiana benthamiana cells. This study provides valuable information on the role of CitYTHs in the signaling pathways involved in environmental stress responses in Citrus.

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