scholarly journals Circular RNAs in the ageing African turquoise killifish

2019 ◽  
Author(s):  
Franziska Metge ◽  
Yumi Kim ◽  
Jorge Boucas ◽  
Christoph Dieterich ◽  
Dario Riccardo Valenzano
Keyword(s):  
Covalent Bond ◽  
Circular Rnas ◽  
Splice Donor ◽  
Specific Expression ◽  
Splice Isoforms ◽  
Protein Coding ◽  
Nothobranchius Furzeri ◽  
Circular Molecule ◽  
Time Specific ◽  
Host Genes

AbstractCircRNAs are a subgroup of RNAs which form a circular molecule. During the splicing process the 3’ splice donor loops back to form a covalent bond with an upstream 5’ splice acceptor instead of the downstream 5’ acceptor. The majority of circRNAs are non-coding splice isoforms of protein coding genes showing tissue and time specific expression. Because circRNAs have no 5’ cap nor 3’ poly-A tail, they degrade slower than their linear host genes. Only few studies were able to show a specific function for circRNAs.In this work we sequenced 23 samples from three tissues (brain, muscle, and gut) at three (two for gut) time points throughout the life of the naturally short-lived African turquoise killifish (Nothobranchius furzeri). We identified 1810 unique circRNAs, half of which are conserved with humans and mice. With this study we provide a comprehensive atlas to the circRNA landscape in the ageing African turquoise killifish, which serves as a novel resource to the circRNA as well as the ageing community.

scholarly journals Closing the circle: current state and perspectives of circular RNA databases

2020 ◽  
Author(s):  
Marieke Vromman ◽  
Jo Vandesompele ◽  
Pieter-Jan Volders
Keyword(s):  
Splice Junction ◽  
Circular Rna ◽  
Circular Rnas ◽  
Working Mechanism ◽  
Comprehensive Overview ◽  
Specific Expression ◽  
Protein Coding ◽  
Rna Molecules ◽  
Current State ◽  
Coding Potential

Abstract Circular RNAs (circRNAs) are covalently closed RNA molecules that have been linked to various diseases, including cancer. However, a precise function and working mechanism are lacking for the larger majority. Following many different experimental and computational approaches to identify circRNAs, multiple circRNA databases were developed as well. Unfortunately, there are several major issues with the current circRNA databases, which substantially hamper progression in the field. First, as the overlap in content is limited, a true reference set of circRNAs is lacking. This results from the low abundance and highly specific expression of circRNAs, and varying sequencing methods, data-analysis pipelines, and circRNA detection tools. A second major issue is the use of ambiguous nomenclature. Thus, redundant or even conflicting names for circRNAs across different databases contribute to the reproducibility crisis. Third, circRNA databases, in essence, rely on the position of the circRNA back-splice junction, whereas alternative splicing could result in circRNAs with different length and sequence. To uniquely identify a circRNA molecule, the full circular sequence is required. Fourth, circRNA databases annotate circRNAs’ microRNA binding and protein-coding potential, but these annotations are generally based on presumed circRNA sequences. Finally, several databases are not regularly updated, contain incomplete data or suffer from connectivity issues. In this review, we present a comprehensive overview of the current circRNA databases and their content, features, and usability. In addition to discussing the current issues regarding circRNA databases, we come with important suggestions to streamline further research in this growing field.

scholarly journals Regulatory Effects of Circular RNAs on Host Genes in Human Cancer

2021 ◽  
Vol 10 ◽  
Author(s):  
Xiong Wang ◽  
Huijun Li ◽  
Yanjun Lu ◽  
Liming Cheng
Keyword(s):  
Cancer Progression ◽  
Closed Loop ◽  
Human Cancer ◽  
Expression Patterns ◽  
Circular Rnas ◽  
Therapeutic Resistance ◽  
Specific Expression ◽  
Protein Scaffold ◽  
Regulatory Effects ◽  
Host Genes

Circular RNAs (circRNAs) are a class of single-stranded, covalent closed-loop RNAs with tissue-/development-specific expression patterns. circRNAs are stable and play oncogenic or tumor suppressive roles in various aspects of cancer, including tumorigenesis, proliferation, apoptosis, metastasis, invasion, chemo-therapeutic resistance, and prognosis. circRNAs act as miRNA/protein sponges, protein scaffold, or template for translation. Increasing evidence shows circRNAs contribute to cancer progression via modulating the expression or function of their host genes. In this review, we summarize the latest progress in the regulation of host genes by circRNAs in human cancer. The works on circRNAs mediated regulation of host genes enhance us to understand the interaction between circRNAs and their host genes in human cancer.

scholarly journals Sex-Biased lncRNA Signature in Fetal Growth Restriction (FGR)

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 921
Author(s):  
Aleksandra Lipka ◽  
Jan Pawel Jastrzebski ◽  
Lukasz Paukszto ◽  
Karol Gustaw Makowczenko ◽  
Elzbieta Lopienska-Biernat ◽  
...  
Keyword(s):  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Target Genes ◽  
Active Regions ◽  
Bioinformatic Analysis ◽  
Growth Restriction ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Differential Analysis ◽  
Protein Coding

Impaired fetal growth is one of the most important causes of prematurity, stillbirth and infant mortality. The pathogenesis of idiopathic fetal growth restriction (FGR) is poorly understood but is thought to be multifactorial and comprise a range of genetic causes. This research aimed to investigate non-coding RNAs (lncRNAs) in the placentas of male and female fetuses affected by FGR. RNA-Seq data were analyzed to detect lncRNAs, their potential target genes and circular RNAs (circRNAs); a differential analysis was also performed. The multilevel bioinformatic analysis enabled the detection of 23,137 placental lncRNAs and 4263 of them were classified as novel. In FGR-affected female fetuses’ placentas (ff-FGR), among 19 transcriptionally active regions (TARs), five differentially expressed lncRNAs (DELs) and 12 differentially expressed protein-coding genes (DEGs) were identified. Within 232 differentially expressed TARs identified in male fetuses (mf-FGR), 33 encompassed novel and 176 known lncRNAs, and 52 DEGs were upregulated, while 180 revealed decreased expression. In ff-FGR ACTA2-AS1, lncRNA expression was significantly correlated with five DEGs, and in mf-FGR, 25 TARs were associated with DELs correlated with 157 unique DEGs. Backsplicing circRNA processes were detected in the range of H19 lncRNA, in both ff- and mf-FGR placentas. The performed global lncRNAs characteristics in terms of fetal sex showed dysregulation of DELs, DEGs and circRNAs that may affect fetus growth and pregnancy outcomes. In female placentas, DELs and DEGs were associated mainly with the vasculature, while in male placentas, disturbed expression predominantly affected immune processes.

scholarly journals Circular RNAs in Sudden Cardiac Death Related Diseases: Novel Biomarker for Clinical and Forensic Diagnosis

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1155
Author(s):  
Meihui Tian ◽  
Zhipeng Cao ◽  
Hao Pang
Keyword(s):  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Early Stage ◽  
Diagnostic Value ◽  
Circular Rnas ◽  
Cardiac Damage ◽  
Postmortem Diagnosis ◽  
Specific Expression ◽  
Forensic Practice ◽  
Artery Disease

The prevention and diagnosis of sudden cardiac death (SCD) are among the most important keystones and challenges in clinical and forensic practice. However, the diagnostic value of the current biomarkers remains unresolved issues. Therefore, novel diagnostic biomarkers are urgently required to identify patients with early-stage cardiovascular diseases (CVD), and to assist in the postmortem diagnosis of SCD cases without typical cardiac damage. An increasing number of studies show that circular RNAs (circRNAs) have stable expressions in myocardial tissue, and their time- and tissue-specific expression levels might reflect the pathophysiological status of the heart, which makes them potential CVD biomarkers. In this article, we briefly introduced the biogenesis and functional characteristics of circRNAs. Moreover, we described the roles of circRNAs in multiple SCD-related diseases, including coronary artery disease (CAD), myocardial ischemia or infarction, arrhythmia, cardiomyopathy, and myocarditis, and discussed the application prospects and challenges of circRNAs as a novel biomarker in the clinical and forensic diagnosis of SCD.

scholarly journals Function of Circular RNAs in Fish and Their Potential Application as Biomarkers

2021 ◽  
Vol 22 (13) ◽  
pp. 7119
Author(s):  
Golam Rbbani ◽  
Artem Nedoluzhko ◽  
Jorge Galindo-Villegas ◽  
Jorge M. O. Fernandes
Keyword(s):  
Growth Regulation ◽  
Functional Characterization ◽  
Circular Rnas ◽  
Farmed Fish ◽  
Developmentally Regulated ◽  
Specific Expression ◽  
Cell Type Specific Expression ◽  
Cell Type Specific ◽  
Taxonomic Groups ◽  
And Function

Circular RNAs (circRNAs) are an emerging class of regulatory RNAs with a covalently closed-loop structure formed during pre-mRNA splicing. Recent advances in high-throughput RNA sequencing and circRNA-specific computational tools have driven the development of novel approaches to their identification and functional characterization. CircRNAs are stable, developmentally regulated, and show tissue- and cell-type-specific expression across different taxonomic groups. They play a crucial role in regulating various biological processes at post-transcriptional and translational levels. However, the involvement of circRNAs in fish immunity has only recently been recognized. There is also broad evidence in mammals that the timely expression of circRNAs in muscle plays an essential role in growth regulation but our understanding of their expression and function in teleosts is still very limited. Here, we discuss the available knowledge about circRNAs and their role in growth and immunity in vertebrates from a comparative perspective, with emphasis on cultured teleost fish. We expect that the interest in teleost circRNAs will increase substantially soon, and we propose that they may be used as biomarkers for selective breeding of farmed fish, thus contributing to the sustainability of the aquaculture sector.

scholarly journals Annotation of snoRNA abundance across human tissues reveals complex snoRNA-host gene relationships

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Étienne Fafard-Couture ◽  
Danny Bergeron ◽  
Sonia Couture ◽  
Sherif Abou-Elela ◽  
Michelle S. Scott
Keyword(s):  
Housekeeping Genes ◽  
Host Gene ◽  
Rna Modification ◽  
Human Tissues ◽  
Rna Seq ◽  
Healthy Human ◽  
Protein Coding ◽  
Conservation Level ◽  
Nucleolar Rnas ◽  
Host Genes

Abstract Background Small nucleolar RNAs (snoRNAs) are mid-size non-coding RNAs required for ribosomal RNA modification, implying a ubiquitous tissue distribution linked to ribosome synthesis. However, increasing numbers of studies identify extra-ribosomal roles of snoRNAs in modulating gene expression, suggesting more complex snoRNA abundance patterns. Therefore, there is a great need for mapping the snoRNome in different human tissues as the blueprint for snoRNA functions. Results We used a low structure bias RNA-Seq approach to accurately quantify snoRNAs and compare them to the entire transcriptome in seven healthy human tissues (breast, ovary, prostate, testis, skeletal muscle, liver, and brain). We identify 475 expressed snoRNAs categorized in two abundance classes that differ significantly in their function, conservation level, and correlation with their host gene: 390 snoRNAs are uniformly expressed and 85 are enriched in the brain or reproductive tissues. Most tissue-enriched snoRNAs are embedded in lncRNAs and display strong correlation of abundance with them, whereas uniformly expressed snoRNAs are mostly embedded in protein-coding host genes and are mainly non- or anticorrelated with them. Fifty-nine percent of the non-correlated or anticorrelated protein-coding host gene/snoRNA pairs feature dual-initiation promoters, compared to only 16% of the correlated non-coding host gene/snoRNA pairs. Conclusions Our results demonstrate that snoRNAs are not a single homogeneous group of housekeeping genes but include highly regulated tissue-enriched RNAs. Indeed, our work indicates that the architecture of snoRNA host genes varies to uncouple the host and snoRNA expressions in order to meet the different snoRNA abundance levels and functional needs of human tissues.

scholarly journals Non-Coding RNAs in Breast Cancer: Intracellular and Intercellular Communication

2018 ◽  
Vol 4 (4) ◽  
pp. 40 ◽  
Author(s):  
Carolyn Klinge
Keyword(s):  
Breast Cancer ◽  
Intercellular Communication ◽  
Intracellular Signaling ◽  
Colorectal Neoplasia ◽  
Breast Tumors ◽  
Estrogen Receptor Α ◽  
Circular Rnas ◽  
Intercellular Signaling ◽  
Protein Coding ◽  
Non Coding Rnas

Non-coding RNAs (ncRNAs) are regulators of intracellular and intercellular signaling in breast cancer. ncRNAs modulate intracellular signaling to control diverse cellular processes, including levels and activity of estrogen receptor α (ERα), proliferation, invasion, migration, apoptosis, and stemness. In addition, ncRNAs can be packaged into exosomes to provide intercellular communication by the transmission of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) to cells locally or systemically. This review provides an overview of the biogenesis and roles of ncRNAs: small nucleolar RNA (snRNA), circular RNAs (circRNAs), PIWI-interacting RNAs (piRNAs), miRNAs, and lncRNAs in breast cancer. Since more is known about the miRNAs and lncRNAs that are expressed in breast tumors, their established targets as oncogenic drivers and tumor suppressors will be reviewed. The focus is on miRNAs and lncRNAs identified in breast tumors, since a number of ncRNAs identified in breast cancer cells are not dysregulated in breast tumors. The identity and putative function of selected lncRNAs increased: nuclear paraspeckle assembly transcript 1 (NEAT1), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), steroid receptor RNA activator 1 (SRA1), colon cancer associated transcript 2 (CCAT2), colorectal neoplasia differentially expressed (CRNDE), myocardial infarction associated transcript (MIAT), and long intergenic non-protein coding RNA, Regulator of Reprogramming (LINC-ROR); and decreased levels of maternally-expressed 3 (MEG3) in breast tumors have been observed as well. miRNAs and lncRNAs are considered targets of therapeutic intervention in breast cancer, but further work is needed to bring the promise of regulating their activities to clinical use.

scholarly journals Dysregulated circular RNAs in medulloblastoma regulate proliferation and growth of tumor cells via host genes

2018 ◽  
Vol 7 (12) ◽  
pp. 6147-6157 ◽  
Author(s):  
Tao Lv ◽  
Yi-Feng Miao ◽  
Ke Jin ◽  
Shuo Han ◽  
Tian-Qi Xu ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circular Rnas ◽  
Growth Of Tumor ◽  
Host Genes

scholarly journals Predicting cell-cycle expressed genes identifies canonical and non-canonical regulators of time-specific expression in Saccharomyces cerevisiae

2018 ◽  
Author(s):  
Nicholas L Panchy ◽  
John P. Lloyd ◽  
Shin-Han Shiu
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Target Genes ◽  
Specific Cell ◽  
Data Sets ◽  
Cell Cycle Regulators ◽  
Specific Expression ◽  
Regulatory Data ◽  
Time Specific ◽  
Cycle Regulation

AbstractThe collection all TFs, target genes and their interactions in an organism form a gene regulatory network (GRN), which underly complex patterns of transcription even in unicellular species. However, identifying which interactions regulate expression in a specific temporal context remains a challenging task. With multiple experimental and computational approaches to characterize GRNs, we predicted general and phase-specific cell-cycle expression in Saccharomyces cerevisiae using four regulatory data sets: chromatin immunoprecipitation (ChIP), TF deletion data (Deletion), protein binding microarrays (PBMs), and position weight matrices (PWMs). Our results indicate that the source of regulatory interaction information significantly impacts our ability to predict cell-cycle expression where the best model was constructed by combining selected TF features from ChIP and Deletion data as well as TF-TF interaction features in the form of feed-forward loops. The TFs that were the best predictors of cell-cycle expression were enriched for known cell-cycle regulators but also include regulators not implicated in cell-cycle regulation previously. In addition, ChIP and Deletion datasets led to the identification different subsets of TFs important for predicting cell-cycle expression. Finally, analysis of important TF-TF interaction features suggests that the GRN regulating cell cycle expression is highly interconnected and clustered around four groups of genes, two of which represent known cell-cycle regulatory complexes, while the other two contain TFs that are not known cell-cycle regulators (Ste12-Tex1 and Rap1-Hap1-Msn4), but are nonetheless important to regulating the timing of expression. Thus, not only do our models accurately reflect what is known about the regulation of the S. cerevisiae cell cycle, they can be used to discover regulatory factors which play a role in controlling expression during the cell cycle as well as other contexts with discrete temporal patterns of expression.

scholarly journals Circular RNAs as Novel Diagnostic Biomarkers and Therapeutic Targets in Kidney Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Jianwen Yu ◽  
Danli Xie ◽  
Naya Huang ◽  
Qin Zhou
Keyword(s):  
Kidney Disease ◽  
Kidney Diseases ◽  
Expression Patterns ◽  
Therapeutic Targets ◽  
Kidney Injury ◽  
Renal Diseases ◽  
Circular Rnas ◽  
Specific Expression ◽  
Glomerular Diseases ◽  
Diagnosis And Prognosis

Circular RNAs (circRNAs) are a novel type of non-coding RNAs that have aroused growing attention in this decade. They are widely expressed in eukaryotes and generally have high stability owing to their special closed-loop structure. Many circRNAs are abundant, evolutionarily conserved, and exhibit cell-type-specific and tissue-specific expression patterns. Mounting evidence suggests that circRNAs have regulatory potency for gene expression by acting as microRNA sponges, interacting with proteins, regulating transcription, or directly undergoing translation. Dysregulated expression of circRNAs were found in many pathological conditions and contribute to the pathogenesis and progression of various disorders, including renal diseases. Recent studies have revealed that circRNAs may serve as novel reliable biomarkers for the diagnosis and prognosis prediction of multiple kidney diseases, such as renal cell carcinoma (RCC), acute kidney injury (AKI), diabetic kidney disease (DKD), and other glomerular diseases. Furthermore, circRNAs expressed by intrinsic kidney cells are shown to play a substantial role in kidney injury, mostly reported in DKD and RCC. Herein, we review the biogenesis and biological functions of circRNAs, and summarize their roles as promising biomarkers and therapeutic targets in common kidney diseases.

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