scholarly journals Genome-Wide Investigation and Functional Analysis of Sus scrofa RNA Editing Sites across Eleven Tissues

Genes ◽  
2019 ◽  
Vol 10 (5) ◽  
pp. 327 ◽  
Author(s):  
Zishuai Wang ◽  
Xikang Feng ◽  
Zhonglin Tang ◽  
Shuai Cheng Li
Keyword(s):  
Rna Editing ◽  
Sus Scrofa ◽  
Sequencing Data ◽  
Coding Regions ◽  
Genome Wide ◽  
Model Animal ◽  
High Enrichment ◽  
The Impact ◽  
Sequence Characteristics ◽  
Editing Level

Recently, the prevalence and importance of RNA editing have been illuminated in mammals. However, studies on RNA editing of pigs, a widely used biomedical model animal, are rare. Here we collected RNA sequencing data across 11 tissues and identified more than 490,000 RNA editing sites. We annotated their biological features, detected flank sequence characteristics of A-to-I editing sites and the impact of A-to-I editing on miRNA–mRNA interactions, and identified RNA editing quantitative trait loci (edQTL). Sus scrofa RNA editing sites showed high enrichment in repetitive regions with a median editing level as 15.38%. Expectedly, 96.3% of the editing sites located in non-coding regions including intron, 3′ UTRs, intergenic, and gene proximal regions. There were 2233 editing sites located in the coding regions and 980 of them caused missense mutation. Our results indicated that to an A-to-I editing site, the adjacent four nucleotides, two before it and two after it, have a high impact on the editing occurrences. A commonly observed editing motif is CCAGG. We found that 4552 A-to-I RNA editing sites could disturb the original binding efficiencies of miRNAs and 4176 A-to-I RNA editing sites created new potential miRNA target sites. In addition, we performed edQTL analysis and found that 1134 edQTLs that significantly affected the editing levels of 137 RNA editing sites. Finally, we constructed PRESDB, the first pig RNA editing sites database. The site provides necessary functions associated with Sus scrofa RNA editing study.

scholarly journals A porcine brain-wide RNA editing landscape

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Jinrong Huang ◽  
Lin Lin ◽  
Zhanying Dong ◽  
Ling Yang ◽  
Tianyu Zheng ◽  
...  
Keyword(s):  
Rna Editing ◽  
Repetitive Sequences ◽  
Brain Regions ◽  
Mammalian Brain ◽  
Protein Coding ◽  
Coding Regions ◽  
Pig Brain ◽  
Genome Wide ◽  
A Genome ◽  
Editing Level

AbstractAdenosine-to-inosine (A-to-I) RNA editing, catalyzed by ADAR enzymes, is an essential post-transcriptional modification. Although hundreds of thousands of RNA editing sites have been reported in mammals, brain-wide analysis of the RNA editing in the mammalian brain remains rare. Here, a genome-wide RNA-editing investigation is performed in 119 samples, representing 30 anatomically defined subregions in the pig brain. We identify a total of 682,037 A-to-I RNA editing sites of which 97% are not identified before. Within the pig brain, cerebellum and olfactory bulb are regions with most edited transcripts. The editing level of sites residing in protein-coding regions are similar across brain regions, whereas region-distinct editing is observed in repetitive sequences. Highly edited conserved recoding events in pig and human brain are found in neurotransmitter receptors, demonstrating the evolutionary importance of RNA editing in neurotransmission functions. Although potential data biases caused by age, sex or health status are not considered, this study provides a rich resource to better understand the evolutionary importance of post-transcriptional RNA editing.

Genome wide quantification of A-to-I RNA editing activity

2019 ◽  
Author(s):  
Shalom Hillel Roth ◽  
Erez Y. Levanon ◽  
Eli Eisenberg
Keyword(s):  
Rna Editing ◽  
Innate Immune ◽  
Rna Modification ◽  
Immune Disorders ◽  
Computational Tool ◽  
Genome Wide ◽  
Editing Activity ◽  
Single Number ◽  
Editing Level

Abstract Adenosine to inosine (A-to-I) RNA editing by the ADAR enzymes is a common RNA modification, preventing false activation of the innate immune system by endogenous dsRNAs. Methods for quantification of ADAR activity are sought after, due to an increasing interest in the role of ADARs in cancer and auto-immune disorders, as well as attempts to harness the ADAR enzymes for RNA engineering. Here we present the Alu Editing Index (AEI), a robust and simple-to-use computational tool devised for this purpose that produces a single number representing the global editing level from BAM files. The AEI tool is available at https://github.com/a2iEditing/RNAEditingIndexer

A porcine brain-wide RNA editing landscape

2020 ◽  
Author(s):  
Jinrong Huang ◽  
Lin Lin ◽  
Zhanying Dong ◽  
Ling Yang ◽  
Tianyu Zheng ◽  
...  
Keyword(s):  
Rna Editing ◽  
Repetitive Sequences ◽  
Brain Regions ◽  
Mammalian Brain ◽  
Protein Coding ◽  
Porcine Brain ◽  
Coding Regions ◽  
Pig Brain ◽  
Genome Wide ◽  
A Genome

Abstract Adenosine-to-inosine (A-to-I) RNA editing, catalyzed by ADAR enzymes, is an essential post-transcriptional modification. Although hundreds of thousands of RNA editing sites have been reported in mammals, brain-wide analysis of the RNA editing in the mammalian brain remains rare. Here, a genome-wide RNA editing investigation is performed in 119 samples, representing 30 anatomically defined subregions in the pig brain. We identify a total of 682,037 A-to-I RNA editing sites of which 97% are not identified before. Within the pig brain, cerebellum and olfactory bulb are regions with most edited transcripts. The editing level of sites residing in protein-coding regions are similar across brain regions, whereas region-distinct editing is observed in repetitive sequences. Highly edited conserved recoding events in pig and human brain are found in neurotransmitter receptors, demonstrating the evolutionary importance of RNA editing in neurotransmission functions. The porcine brain-wide RNA landscape provides a rich resource to better understand the evolutionally importance of post-transcriptional RNA editing.

scholarly journals Developmental atlas of the RNA editome in Sus scrofa skeletal muscle

DNA Research ◽  
2019 ◽  
Vol 26 (3) ◽  
pp. 261-272 ◽  
Author(s):  
Yalan Yang ◽  
Min Zhu ◽  
Xinhao Fan ◽  
Yilong Yao ◽  
Junyu Yan ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Rna Editing ◽  
Sus Scrofa ◽  
Muscle Development ◽  
Rna Seq ◽  
Sequencing Data ◽  
Adenosine Deaminases ◽  
Bisulphite Sequencing ◽  
Highly Correlated ◽  
Gain Loss

AbstractAdenosine-to-inosine (A-to-I) RNA editing meditated by adenosine deaminases acting on RNA (ADARs) enzymes is a widespread post-transcriptional event in mammals. However, A-to-I editing in skeletal muscle remains poorly understood. By integrating strand-specific RNA-seq, whole genome bisulphite sequencing, and genome sequencing data, we comprehensively profiled the A-to-I editome in developing skeletal muscles across 27 prenatal and postnatal stages in pig, an important farm animal and biomedical model. We detected 198,892 A-to-I editing sites and found that they occurred more frequently at prenatal stages and showed low conservation among pig, human, and mouse. Both the editing level and frequency decreased during development and were positively correlated with ADAR enzymes expression. The hyper-edited genes were functionally related to the cell cycle and cell division. A co-editing module associated with myogenesis was identified. The developmentally differential editing sites were functionally enriched in genes associated with muscle development, their editing levels were highly correlated with expression of their host mRNAs, and they potentially influenced the gain/loss of miRNA binding sites. Finally, we developed a database to visualize the Sus scrofa RNA editome. Our study presents the first profile of the dynamic A-to-I editome in developing animal skeletal muscle and provides evidences that RNA editing is a vital regulator of myogenesis.

scholarly journals Evidence for Transcriptome-wide RNA Editing Among Sus scrofa PRE-1 SINE Elements

2017 ◽  
Author(s):  
Scott A. Funkhouser ◽  
Juan P. Steibel ◽  
Ronald O. Bates ◽  
Nancy E. Raney ◽  
Darius Schenk ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Transcriptional Regulation ◽  
Rna Editing ◽  
High Throughput ◽  
Sus Scrofa ◽  
Sequence Data ◽  
Rna Sequences ◽  
Editing Event ◽  
Coding Regions ◽  
Dna And Rna

AbstractBackgroundRNA editing by ADAR (adenosine deaminase acting on RNA) proteins is a form of transcriptional regulation that is widespread among humans and other primates. Based on high-throughput scans used to identify putative RNA editing sites, ADAR appears to catalyze a substantial number of adenosine to inosine transitions within repetitive regions of the primate transcriptome, thereby dramatically enhancing genetic variation beyond what is encoded in the genome.ResultsHere, we demonstrate the editing potential of the pig transcriptome by utilizing DNA and RNA sequence data from the same pig. We identified a total of 8550 mismatches between DNA and RNA sequences across three tissues, with 75% of these exhibiting an A-to-G (DNA to RNA) discrepancy, indicative of a canonical ADAR-catalyzed RNA editing event. When we consider only mismatches within repetitive regions of the genome, the A-to-G percentage increases to 94%, with the majority of these located within the swine specific SINE retrotransposon PRE-1. We also observe evidence of A-to-G editing within coding regions that were previously verified in primates.ConclusionsThus, our high-throughput evidence suggests that pervasive RNA editing by ADAR can exist outside of the primate lineage to dramatically enhance genetic variation in pigs.

scholarly journals Mitochondrial DNAs provide insight into trypanosome phylogeny and molecular evolution

2020 ◽  
Author(s):  
Christopher Kay ◽  
Tom A Williams ◽  
Wendy Gibson
Keyword(s):  
Mitochondrial Dna ◽  
Molecular Evolution ◽  
Trypanosoma Brucei ◽  
Rna Editing ◽  
Sub Saharan Africa ◽  
Coding Regions ◽  
Gene Coding ◽  
Animal Pathogens ◽  
Recent Emergence ◽  
The Impact

Abstract Background: Trypanosomes are single-celled eukaryotic parasites characterised by the unique biology of their mitochondrial DNA. African livestock trypanosomes impose a major burden on agriculture across sub-Saharan Africa, but are poorly understood compared to those that cause sleeping sickness and Chagas disease in humans. Here we explore the potential of the maxicircle, a component of trypanosome mitochondrial DNA to study the evolutionary history of trypanosomes.Results: We used long-read sequencing to completely assemble maxicircle mitochondrial DNA from four previously uncharacterized African trypanosomes, and leveraged these assemblies to scaffold and assemble a further 103 trypanosome maxicircle gene coding regions from published short-read data. While synteny was largely conserved, there were repeated, independent losses of Complex I genes. Comparison of pre-edited and non-edited genes revealed the impact of RNA editing on nucleotide composition, with non-edited genes approaching the limits of GC loss. African tsetse-transmitted trypanosomes showed high levels of RNA editing compared to other trypanosomes. The gene coding regions of maxicircle mitochondrial DNAswere used to construct time-resolved phylogenetic trees, revealing deep divergence events among isolates of the pathogens Trypanosoma brucei and T. congolense. Conclusions: Our data represents a new resource for experimental and evolutionary analyses of trypanosome phylogeny, molecular evolution and function. Molecular clock analyses yielded a timescale for trypanosome evolution congruent with major biogeographical events in Africa and revealed the recent emergence of Trypanosoma brucei gambiense and T. equiperdum, major human and animal pathogens.

scholarly journals Genome-Wide Investigation and Functional Analysis of Sus scrofa RNA Editing Sites across Eleven Tissues

Genes ◽  
2019 ◽  
Vol 10 (7) ◽  
pp. 520
Author(s):  
Wang ◽  
Feng ◽  
Tang ◽  
Li
Keyword(s):  
Functional Analysis ◽  
Rna Editing ◽  
Sus Scrofa ◽  
Genome Wide

Two errors occurred in the References part of our paper [...]

scholarly journals Genome-wide characterization of RNA editing in chicken: lack of evidence for non-A-to-I events

2014 ◽  
Author(s):  
Laure Frésard ◽  
Sophie Leroux ◽  
Pierre-François Roux ◽  
C Klopp ◽  
Stéphane Fabre ◽  
...  
Keyword(s):  
Rna Editing ◽  
High Throughput Sequencing ◽  
Nucleotide Substitutions ◽  
Sequencing Technologies ◽  
Genome Wide ◽  
Level Increase ◽  
Functional Consequences ◽  
Genome Screening ◽  
Editing Level

RNA editing corresponds to a post-transcriptional nucleotide change in the RNA sequence, creating an alternative nucleotide, not present in the DNA sequence. This leads to a diversification of transcription products with potential functional consequences. Two nucleotide substitutions are mainly described in animals, from adenosine to inosine (A-to-I) and from cytidine to uridine (C-to-U). This phenomenon is more and more described in mammals, notably since the availability of next generation sequencing technologies allowing a whole genome screening of RNA-DNA differences. The number of studies recording RNA editing in other vertebrates like chicken are still limited. We chose to use high throughput sequencing technologies to search for RNA editing in chicken, to understand to what extent this phenomenon is conserved in vertebrates. We performed RNA and DNA sequencing from 8 embryos. Being aware of common pitfalls inherent to sequence analyses leading to false positive discovery, we stringently filtered our datasets and found less than 40 reliable candidates. Conservation of particular sites of RNA editing was attested by the presence of 3 edited sites previously detected in mammals. We then characterized editing levels for selected candidates in several tissues and at different time points, from 4.5 days of embryonic development to adults, and observed a clear tissue-specificity and a gradual editing level increase with time. By characterizing the RNA editing landscape in chicken, our results highlight the extent of evolutionary conservation of this phenomenon within vertebrates, and provide support of an absence of non A-to-I events from the chicken transcriptome.

scholarly journals RNA editing-based classification of diffuse gliomas: predicting isocitrate dehydrogenase mutation and chromosome 1p/19q codeletion

2019 ◽  
Vol 20 (S19) ◽  
Author(s):  
Sean Chun-Chang Chen ◽  
Chung-Ming Lo ◽  
Shih-Hua Wang ◽  
Emily Chia-Yu Su
Keyword(s):  
Random Forest ◽  
Rna Editing ◽  
Isocitrate Dehydrogenase ◽  
Prediction Models ◽  
Machine Learning Algorithms ◽  
Support Vector ◽  
Genome Wide ◽  
Diffuse Gliomas ◽  
Editing Level

Abstract Background Accurate classification of diffuse gliomas, the most common tumors of the central nervous system in adults, is important for appropriate treatment. However, detection of isocitrate dehydrogenase (IDH) mutation and chromosome1p/19q codeletion, biomarkers to classify gliomas, is time- and cost-intensive and diagnostic discordance remains an issue. Adenosine to inosine (A-to-I) RNA editing has emerged as a novel cancer prognostic marker, but its value for glioma classification remains largely unexplored. We aim to (1) unravel the relationship between RNA editing and IDH mutation and 1p/19q codeletion and (2) predict IDH mutation and 1p/19q codeletion status using machine learning algorithms. Results By characterizing genome-wide A-to-I RNA editing signatures of 638 gliomas, we found that tumors without IDH mutation exhibited higher total editing level compared with those carrying it (Kolmogorov-Smirnov test, p < 0.0001). When tumor grade was considered, however, only grade IV tumors without IDH mutation exhibited higher total editing level. According to 10-fold cross-validation, support vector machines (SVM) outperformed random forest and AdaBoost (DeLong test, p < 0.05). The area under the receiver operating characteristic curve (AUC) of SVM in predicting IDH mutation and 1p/19q codeletion were 0.989 and 0.990, respectively. After performing feature selection, AUCs of SVM and AdaBoost in predicting IDH mutation were higher than that of random forest (0.985 and 0.983 vs. 0.977; DeLong test, p < 0.05), but AUCs of the three algorithms in predicting 1p/19q codeletion were similar (0.976–0.982). Furthermore, 67% of the six continuously misclassified samples by our 1p/19q codeletion prediction models were misclassifications in the original labelling after inspection of 1p/19q status and/or pathology report, highlighting the accuracy and clinical utility of our models. Conclusions The study represents the first genome-wide analysis of glioma editome and identifies RNA editing as a novel prognostic biomarker for glioma. Our prediction models provide standardized, accurate, reproducible and objective classification of gliomas. Our models are not only useful in clinical decision-making, but also able to identify editing events that have the potential to serve as biomarkers and therapeutic targets in glioma management and treatment.

scholarly journals Mitochondrial DNAs provide insight into trypanosome phylogeny and molecular evolution

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
C. Kay ◽  
T. A. Williams ◽  
W. Gibson
Keyword(s):  
Mitochondrial Dna ◽  
Molecular Evolution ◽  
Trypanosoma Brucei ◽  
Rna Editing ◽  
Sub Saharan Africa ◽  
Coding Regions ◽  
Gene Coding ◽  
Animal Pathogens ◽  
Mitochondrial Dnas ◽  
The Impact

Abstract Background Trypanosomes are single-celled eukaryotic parasites characterised by the unique biology of their mitochondrial DNA. African livestock trypanosomes impose a major burden on agriculture across sub-Saharan Africa, but are poorly understood compared to those that cause sleeping sickness and Chagas disease in humans. Here we explore the potential of the maxicircle, a component of trypanosome mitochondrial DNA to study the evolutionary history of trypanosomes. Results We used long-read sequencing to completely assemble maxicircle mitochondrial DNA from four previously uncharacterized African trypanosomes, and leveraged these assemblies to scaffold and assemble a further 103 trypanosome maxicircle gene coding regions from published short-read data. While synteny was largely conserved, there were repeated, independent losses of Complex I genes. Comparison of pre-edited and non-edited genes revealed the impact of RNA editing on nucleotide composition, with non-edited genes approaching the limits of GC loss. African tsetse-transmitted trypanosomes showed high levels of RNA editing compared to other trypanosomes. The gene coding regions of maxicircle mitochondrial DNAs were used to construct time-resolved phylogenetic trees, revealing deep divergence events among isolates of the pathogens Trypanosoma brucei and T. congolense. Conclusions Our data represents a new resource for experimental and evolutionary analyses of trypanosome phylogeny, molecular evolution and function. Molecular clock analyses yielded a timescale for trypanosome evolution congruent with major biogeographical events in Africa and revealed the recent emergence of Trypanosoma brucei gambiense and T. equiperdum, major human and animal pathogens.

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