scholarly journals Transposons modulate transcriptomic and phenotypic variation via the formation of circular RNAs in maize

2017 ◽  
Author(s):  
Lu Chen ◽  
Pei Zhang ◽  
Yuan Fan ◽  
Juan Huang ◽  
Qiong Lu ◽  
...  
Keyword(s):  
Phenotypic Variation ◽  
Genomic Variation ◽  
Circular Rnas ◽  
Maize Genome ◽  
Proof Of Concept ◽  
High Confidence ◽  
Genomic Features ◽  
Rna Molecules ◽  
Expression Variation ◽  
Flanking Regions

AbstractCircular RNAs (circRNAs) are covalently closed, single-stranded RNA molecules. Recent studies in human showed that circRNAs can arise via transcription of reverse complementary pairs of transposons. Given the prevalence of transposons in the maize genome and dramatic genomic variation driven by transposons, we hypothesize that transposons in maize may be involved in the formation of circRNAs and further modulate phenotypic variation. To test our hypothesis, we performed circRNA-Seq on B73 seedling leaves and integrate these data with 977 publicly available mRNA-Seq datasets. We uncovered 1,551 high-confidence maize circRNAs, which show distinct genomic features as compared to linear transcripts. Comprehensive analyses demonstrated that LINE1-like elements (LLE) and their Reverse Complementary Pairs (LLERCPs) are significantly enriched in the flanking regions of circRNAs. Interestingly, the accumulation of circRNA transcripts increases, while the accumulation of linear transcripts decreases as the number of LLERCPs increases. Furthermore, genes with LLERCP-mediated circRNAs are enriched among loci that are associated with phenotypic variation. These results suggest that LLERCPs can modulate phenotypic variation by the formation of circRNAs. As a proof of concept, we showed that the presence/absence variation of LLERCPs could result in expression variation of one cicrRNA, circ352, and further related to plant height through the interaction between circRNA and functional linear transcript. Our first glimpse of circRNAs uncovers a new role for transposons in the modulation of transcriptomic and phenotypic variation via the formation of circRNAs.

scholarly journals Global increase in circRNA levels in myotonic dystrophy

2018 ◽  
Author(s):  
Karol Czubak ◽  
Katarzyna Taylor ◽  
Agnieszka Piasecka ◽  
Krzysztof Sobczak ◽  
Katarzyna Kozlowska ◽  
...  
Keyword(s):  
Myotonic Dystrophy ◽  
Digital Pcr ◽  
Circular Rnas ◽  
Splicing Factors ◽  
Rna Molecules ◽  
Experimental Systems ◽  
Muscle Tissues ◽  
Protein Interactome ◽  
Global Increase ◽  
And Function

AbstractSplicing aberrations induced as a consequence of the sequestration of MBNL splicing factors on the DMPK transcript, which contains expanded CUG repeats, present a major pathomechanism of myotonic dystrophy type 1 (DM1). As MBNLs may also be important factors involved in the biogenesis of circular RNAs (circRNAs), we hypothesized that the level of circRNAs would be decreased in DM1. To test this hypothesis, we selected twenty well-validated circRNAs and analyzed their levels in several experimental systems (e.g., cell lines, DM muscle tissues, and a mouse model of DM1) using droplet digital PCR assays. We also explored the global level of circRNAs using two RNA-Seq datasets of DM1 muscle samples. Contrary to our original hypothesis, our results consistently showed a global increase in circRNA levels in DM1 and we identified numerous circRNAs that were increased in DM1. We also identified many genes (including muscle-specific genes) giving rise to numerous (>10) circRNAs. Thus, this study is the first to show an increase in global circRNA levels in DM1. We also provided preliminary results showing the association of circRNA level with muscle weakness and alternative splicing changes that are biomarkers of DM1 severity.Author SummaryRecently, a great deal of interest has been focused on a new class of RNA molecules called circular RNAs (circRNAs). To date, thousands of circRNAs have been found in different human cells/tissues. Although the function of circRNAs remains mostly unknown, circRNAs have emerged as an important component of the RNA-RNA and RNA-protein interactome. Thus, intensive efforts are being made to fully understand the biology and function of circRNAs, especially their role in human diseases. As an important role in the biogenesis of circRNA may be played by MBNL splicing factors, in this study we used DM1 (to a lesser extent, DM2) as a natural model in which the level of MBNLs is decreased. In contrast to the expected effect, our results consistently showed a global increase in circRNA levels in DM1. As a consequence, whole genome transcriptome analysis revealed dozens of circRNAs with significantly altered (mostly increased) levels in DM1. Furthermore, we observed that the circRNA levels were in many cases strongly associated with DM1 severity.

scholarly journals Enviromic assembly increases accuracy and reduces costs of the genomic prediction for yield plasticity

2021 ◽  
Author(s):  
Germano MF Costa-Neto ◽  
Jose M F Crossa ◽  
Roberto F Fritsche-Neto
Keyword(s):  
Phenotypic Variation ◽  
Field Trials ◽  
Proof Of Concept ◽  
Tropical Maize ◽  
Early Screening ◽  
Environmental Similarity ◽  
Genetic And Environmental Factors ◽  
Growing Conditions ◽  
Algorithm Scheme

Quantitative genetics states that phenotypic variation is a consequence of genetic and environmental factors and their subsequent interaction. Here, we present an enviromic assembly approach, which includes the use of ecophysiology knowledge in shaping environmental relatedness into whole-genome predictions (GP) for plant breeding (referred to as E-GP). We propose that the quality of an environment is defined by the core of environmental typologies (envirotype) and their frequencies, which describe different zones of plant adaptation. From that, we derive markers of environmental similarity cost-effectively. Combined with the traditional genomic sources (e.g., additive and dominance effects), this approach may better represent the putative phenotypic variation across diverse growing conditions (i.e., phenotypic plasticity). Additionally, we couple a genetic algorithm scheme to design optimized multi-environment field trials (MET), combining enviromic assembly and genomic kinships to provide in-silico realizations of the future genotype-environment combinations that must be phenotyped in the field. As a proof-of-concept, we highlight E-GP applications: (1) managing the lack of phenotypic information in training accurate GP models across diverse environments and (2) guiding an early screening for yield plasticity using optimized phenotyping efforts. Our approach was tested using two non-conventional cross-validation schemes to better visualize the benefits of enviromic assembly in sparse experimental networks. Results on tropical maize show that E-GP outperforms benchmark GP in all scenarios and cases tested. We show that for training accurate GP models, the genotype-environment combinations' representativeness is more critical than the MET size. Furthermore, we discuss theoretical backgrounds underlying how the intrinsic envirotype-phenotype covariances within the phenotypic records of (MET) can impact the accuracy of GP and limits the potentialities of predictive breeding approaches. The E-GP is an efficient approach to better use environmental databases to deliver climate-smart solutions, reduce field costs, and anticipate future scenarios.

scholarly journals The Role of Circular RNAs in Keratinocyte Carcinomas

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4240
Author(s):  
Thomas Meyer ◽  
Michael Sand ◽  
Lutz Schmitz ◽  
Eggert Stockfleth
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Circular Rnas ◽  
Mesenchymal Transition ◽  
Rna Molecules ◽  
Factors Associated ◽  
New Therapeutic Approaches ◽  
Non Coding Rna ◽  
Micro Rnas ◽  
Pubmed Search

Keratinocyte carcinomas (KC) include basal cell carcinomas (BCC) and cutaneous squamous cell carcinomas (cSCC) and represents the most common cancer in Europe and North America. Both entities are characterized by a very high mutational burden, mainly UV signature mutations. Predominately mutated genes in BCC belong to the sonic hedgehog pathway, whereas, in cSCC, TP53, CDKN2A, NOTCH1/2 and others are most frequently mutated. In addition, the dysregulation of factors associated with epithelial to mesenchymal transition (EMT) was shown in invasive cSCC. The expression of factors associated with tumorigenesis can be controlled in several ways and include non-coding RNA molecules, such as micro RNAs (miRNA) long noncoding RNAs (lncRNA) and circular RNAs (circRNA). To update findings on circRNA in KC, we reviewed 13 papers published since 2016, identified in a PubMed search. In both BCC and cSCC, numerous circRNAs were identified that were differently expressed compared to healthy skin. Some of them were shown to target miRNAs that are also dysregulated in KC. Moreover, some studies confirmed the biological functions of individual circRNAs involved in cancer development. Thus, circRNAs may be used as biomarkers of disease and disease progression and represent potential targets of new therapeutic approaches for KC.

scholarly journals Transposable elements contribute to dynamic genome content in maize

2019 ◽  
Author(s):  
Sarah N Anderson ◽  
Michelle C Stitzer ◽  
Alex B. Brohammer ◽  
Peng Zhou ◽  
Jaclyn M Noshay ◽  
...  
Keyword(s):  
Transposable Elements ◽  
Genomic Variation ◽  
Gene Content ◽  
Maize Genome ◽  
Large Scope ◽  
Shared Ancestry ◽  
Dynamic Genome ◽  
Genomic Studies ◽  
Genome Assemblies

AbstractTransposable elements (TEs) are ubiquitous components of eukaryotic genomes and can create variation in genomic organization. The majority of maize genomes are composed of TEs. We developed an approach to define shared and variable TE insertions across genome assemblies and applied this method to four maize genomes (B73, W22, Mo17, and PH207). Among these genomes we identified 1.6 Gb of variable TE sequence representing a combination of recent TE movement and deletion of previously existing TEs. Although recent TE movement only accounted for a portion of the TE variability, we identified 4,737 TEs unique to one genome with defined insertion sites in all other genomes. Variable TEs are found for all superfamilies and are distributed across the genome, including in regions of recent shared ancestry among individuals. There are 2,380 genes annotated in the B73 genome located within variable TEs, providing evidence for the role of TEs in contributing to the substantial differences in gene content among these genotypes. The large scope of TE variation present in this limited sample of temperate maize genomes highlights the major contribution of TEs in driving variation in genome organization and gene content.Significance StatementThe majority of the maize genome is comprised of transposable elements (TEs) that have the potential to create genomic variation within species. We developed a method to identify shared and non-shared TEs using whole genome assemblies of four maize inbred lines. Variable TEs are found throughout the maize genome and in comparisons of any two genomes we find ~20% of the genome is due to non-shared TEs. Several thousand maize genes are found within TEs that are variable across lines, highlighting the contribution of TEs to gene content variation. This study creates a comprehensive resource for genomic studies of TE variability among four maize genomes, which will enable studies on the consequences of variable TEs on genome function.

scholarly journals Genome and Transcriptome Sequencing of casper and roy Zebrafish Mutants Provides Novel Genetic Clues for Iridophore Loss

2020 ◽  
Vol 21 (7) ◽  
pp. 2385
Author(s):  
Chao Bian ◽  
Weiting Chen ◽  
Zhiqiang Ruan ◽  
Zhe Hu ◽  
Yu Huang ◽  
...  
Keyword(s):  
Transcriptome Sequencing ◽  
Genetic Basis ◽  
Linkage Disequilibrium Block ◽  
Genomic Variation ◽  
Nucleotide Polymorphisms ◽  
High Confidence ◽  
Genome Maps ◽  
Transcriptional Changes ◽  
Type Ab ◽  
Core Genes

casper has been a widely used transparent mutant of zebrafish. It possesses a combined loss of reflective iridophores and light-absorbing melanophores, which gives rise to its almost transparent trunk throughout larval and adult stages. Nevertheless, genomic causal mutations of this transparent phenotype are poorly defined. To identify the potential genetic basis of this fascinating morphological phenotype, we constructed genome maps by performing genome sequencing of 28 zebrafish individuals including wild-type AB strain, roy orbison (roy), and casper mutants. A total of 4.3 million high-quality and high-confidence homozygous single nucleotide polymorphisms (SNPs) were detected in the present study. We also identified a 6.0-Mb linkage disequilibrium block specifically in both roy and casper that was composed of 39 functional genes, of which the mpv17 gene was potentially involved in the regulation of iridophore formation and maintenance. This is the first report of high-confidence genomic mutations in the mpv17 gene of roy and casper that potentially leads to defective splicing as one major molecular clue for the iridophore loss. Additionally, comparative transcriptomic analyses of skin tissues from the AB, roy and casper groups revealed detailed transcriptional changes of several core genes that may be involved in melanophore and iridophore degeneration. In summary, our updated genome and transcriptome sequencing of the casper and roy mutants provides novel genetic clues for the iridophore loss. These new genomic variation maps will offer a solid genetic basis for expanding the zebrafish mutant database and in-depth investigation into pigmentation of animals.

scholarly journals FcircSEC: An R Package for Full Length circRNA Sequence Extraction and Classification

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Md. Tofazzal Hossain ◽  
Yin Peng ◽  
Shengzhong Feng ◽  
Yanjie Wei
Keyword(s):  
State Of The Art ◽  
Gene Annotation ◽  
R Package ◽  
Full Length ◽  
Circular Rnas ◽  
Prediction Methods ◽  
Rna Molecules ◽  
Prediction Tools

Circular RNAs (circRNAs) are formed by joining the 3′ and 5′ ends of RNA molecules. Identification of circRNAs is an important part of circRNA research. The circRNA prediction methods can predict the circRNAs with start and end positions in the chromosome but cannot identify the full-length circRNA sequences. We present an R package FcircSEC (Full Length circRNA Sequence Extraction and Classification) to extract the full-length circRNA sequences based on gene annotation and the output of any circRNA prediction tools whose output has a chromosome, start and end positions, and a strand for each circRNA. To validate FcircSEC, we have used three databases, circbase, circRNAdb, and plantcircbase. With information such as the chromosome and strand of each circRNA as the input, the identified sequences by FcircSEC are consistent with the databases. The novelty of FcircSEC is that it can take the output of state-of-the-art circRNA prediction tools as input and is applicable for human and other species. We also classify the circRNAs as exonic, intronic, and others. The R package FcircSEC is freely available.

scholarly journals The Emerging Role and Promise of Circular RNAs in Obesity and Related Metabolic Disorders

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1473
Author(s):  
Mohamed Zaiou
Keyword(s):  
Rna Binding ◽  
Metabolic Diseases ◽  
Rna Binding Proteins ◽  
In Vivo Studies ◽  
Future Research ◽  
Circular Rnas ◽  
Exciting Field ◽  
Rna Molecules

Circular RNAs (circRNAs) are genome transcripts that are produced from back-splicing of specific regions of pre-mRNA. These single-stranded RNA molecules are widely expressed across diverse phyla and many of them are stable and evolutionary conserved between species. Growing evidence suggests that many circRNAs function as master regulators of gene expression by influencing both transcription and translation processes. Mechanistically, circRNAs are predicted to act as endogenous microRNA (miRNA) sponges, interact with functional RNA-binding proteins (RBPs), and associate with elements of the transcriptional machinery in the nucleus. Evidence is mounting that dysregulation of circRNAs is closely related to the occurrence of a range of diseases including cancer and metabolic diseases. Indeed, there are several reports implicating circRNAs in cardiovascular diseases (CVD), diabetes, hypertension, and atherosclerosis. However, there is very little research addressing the potential role of these RNA transcripts in the occurrence and development of obesity. Emerging data from in vitro and in vivo studies suggest that circRNAs are novel players in adipogenesis, white adipose browning, obesity, obesity-induced inflammation, and insulin resistance. This study explores the current state of knowledge on circRNAs regulating molecular processes associated with adipogenesis and obesity, highlights some of the challenges encountered while studying circRNAs and suggests some perspectives for future research directions in this exciting field of study.

scholarly journals Non-coding RNAs in kidney injury and repair

2019 ◽  
Vol 317 (2) ◽  
pp. C177-C188 ◽  
Author(s):  
Zhiwen Liu ◽  
Ying Wang ◽  
Shaoqun Shu ◽  
Juan Cai ◽  
Chengyuan Tang ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Cell Injury ◽  
Kidney Injury ◽  
Tubular Epithelial Cell ◽  
Future Research ◽  
Circular Rnas ◽  
Rapid Decline ◽  
Rna Molecules ◽  
Non Coding Rnas ◽  
Injury And Repair

Acute kidney injury (AKI) is a major kidney disease featured by a rapid decline of renal function. Pathologically, AKI is characterized by tubular epithelial cell injury and death. Besides its acute consequence, AKI contributes critically to the development and progression of chronic kidney disease (CKD). After AKI, surviving tubular cells regenerate to repair. Normal repair restores tubular integrity, while maladaptive or incomplete repair results in renal fibrosis and eventually CKD. Non-coding RNAs (ncRNAs) are functional RNA molecules that are transcribed from DNA but not translated into proteins, which mainly include microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), small nucleolar RNAs (snoRNAs), and tRNAs. Accumulating evidence suggests that ncRNAs play important roles in kidney injury and repair. In this review, we summarize the recent advances in the understanding of the roles of ncRNAs, especially miRNAs and lncRNAs in kidney injury and repair, discuss the potential application of ncRNAs as biomarkers of AKI as well as therapeutic targets for treating AKI and impeding AKI-CKD transition, and highlight the future research directions of ncRNAs in kidney injury and repair.

Canine Oil Detection (K9-SCAT) following 2015 Releases from the T/V Arrow Wreck

2017 ◽  
Vol 2017 (1) ◽  
pp. 2620-2641 ◽  
Author(s):  
E.H. Owens ◽  
H.C. Dubach ◽  
P. Bunker ◽  
S. MacDonald ◽  
Z. Yang ◽  
...  
Keyword(s):  
Petroleum Hydrocarbons ◽  
Fuel Oil ◽  
Support Surface ◽  
Chemical Analyses ◽  
Proof Of Concept ◽  
Residual Oil ◽  
High Confidence ◽  
Capability Of Detection ◽  
Trained Observers ◽  
Coverage Rates

Abstract The T/V Arrow sank in 1970, spilling Bunker C fuel oil into Chedabucto Bay, Nova Scotia. In the summer and fall of 2015, residual oil leaked from the sunken vessel and re-oiled shorelines in the Bay. A K9-SCAT field study, funded by Environment and Climate Change Canada (ECCC), was conducted in June 2016 to assess the capability of detection canines to locate stranded oil following the new releases. The canine detected small amounts of weathered surface oil that were barely visible, and in some cases, not visible, to the SCAT-trained observers, as well as subsurface oil on mixed- and coarse-sediment beaches. The average speed of a survey, in terms of the length of shoreline covered, varied depending on the shore type and the width of the survey band. The most challenging site was a steep bedrock shoreline with an alongshore survey rate of 0.2 linear km/hour. Typical alongshore coverage rates for the wide, mixed sediment were in the range 0.7 to 1.2 linear km/hour, and for both straight, wide sand beaches were 1.2 km/hour. The highest alongshore rate was 2.4 linear km/hour for the narrow beach on Janvrin Island. The successful detection of 2015 T/V Arrow cargo oil (both naturally stranded and intentionally planted) on selected Chedabucto Bay shorelines indicates that there is a low risk, high confidence level that the canine did not miss subsurface oil, although that possibility may exist. Where the canine made an alert and no surface oil was visible, chemical analyses of sediment samples indicated that weathered petroleum hydrocarbons were present at those locations and, therefore, the canine had made correct alerts. The results provide further “proof of concept” for K9-SCAT teams to support surface and subsurface oil detection during traditional shoreline assessment surveys.

scholarly journals Assay Optimization and Screening of RNA-Protein Interactions by AlphaScreen

2007 ◽  
Vol 12 (7) ◽  
pp. 946-955 ◽  
Author(s):  
Nicholas L. Mills ◽  
Anang A. Shelat ◽  
R. Kiplin Guy
Keyword(s):  
Drug Discovery ◽  
Small Molecules ◽  
High Throughput ◽  
Protein Interactions ◽  
Proof Of Concept ◽  
Rna Molecules ◽  
Lead Compounds ◽  
Assay Optimization ◽  
Rna Targets ◽  
Hiv 1

The lack of lead compounds that specifically recognize and manipulate the function of RNA molecules limits our ability to consider RNA targets valid for drug discovery. Herein is reported a high-throughput biochemical screen for inhibitors of RNA-protein interactions based on AlphaScreen technology that incorporates several layers of specificity measurements into the primary screen. This screen was used to analyze approximately 5500 compounds from a collection of bioactive small molecules to detect inhibitors of the HIV-1 Rev-RRE and BIV Tat-TAR interactions. This proof-of-concept screen validates the assay as one that accurately identifies hit molecules and determines the selectivity of those hits. ( Journal of Biomolecular Screening 2007: 946-955)

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