scholarly journals RNA editing level in the mouse is determined by the genomic repeat repertoire

RNA ◽  
2006 ◽  
Vol 12 (10) ◽  
pp. 1802-1809 ◽  
Author(s):  
Y. Neeman
Keyword(s):  
Rna Editing ◽  
Genomic Repeat ◽  
Editing Level

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

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 The Reversible Change of GluR2 RNA Editing in Gerbil Hippocampus in Course of Ischemic Tolerance

1999 ◽  
Vol 19 (4) ◽  
pp. 370-375 ◽  
Author(s):  
Kumiko Yamaguchi ◽  
Fuminori Yamaguchi ◽  
Osamu Miyamoto ◽  
Osamu Hatase ◽  
Masaaki Tokuda
Keyword(s):  
Rna Editing ◽  
Ampa Receptor ◽  
Normal Level ◽  
Messenger Rna ◽  
Ischemic Tolerance ◽  
Receptor Desensitization ◽  
Protective Effects ◽  
Reversible Change ◽  
Ca1 Area ◽  
Editing Level

The ischemic tolerance is known to show protective effects on the neurons and the restricted Ca2+ influx through Ca2+ channels might be involved. In α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor, ribonucleic acid (RNA) editing of the GluR2 subunit determines receptor desensitization and Ca2+ permeability. The authors investigated the effect of ischemic tolerance on the messenger RNA editing of Q/R and R/G sites of GluR2 subunit in hippocampus. It was found that the rate of RNA editing in Q/R site showed no change (100% edited), whereas that in R/G site decreased significantly (83.3% normal editing level to 60.4%) at day 3 (preconditioning period) and returned to normal level at day 14 (after preconditioning period). Further investigation revealed that the decrease of editing rate in ischemic tolerance resulted mainly from the decrease of editing in CA1 area.

scholarly journals Adaptive evolution at mRNA editing sites in soft-bodied cephalopods

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10456
Author(s):  
Mikhail Moldovan ◽  
Zoe Chervontseva ◽  
Georgii Bazykin ◽  
Mikhail S. Gelfand
Keyword(s):  
Positive Selection ◽  
Rna Editing ◽  
Editing Site ◽  
Mrna Sequence ◽  
Mrna Editing ◽  
General Role ◽  
Study Selection ◽  
Contextual Characteristics ◽  
Editing Level

Background The bulk of variability in mRNA sequence arises due to mutation—change in DNA sequence which is heritable if it occurs in the germline. However, variation in mRNA can also be achieved by post-transcriptional modification including mRNA editing, changes in mRNA nucleotide sequence that mimic the effect of mutations. Such modifications are not inherited directly; however, as the processes affecting them are encoded in the genome, they have a heritable component, and therefore can be shaped by selection. In soft-bodied cephalopods, adenine-to-inosine RNA editing is very frequent, and much of it occurs at nonsynonymous sites, affecting the sequence of the encoded protein. Methods We study selection regimes at coleoid A-to-I editing sites, estimate the prevalence of positive selection, and analyze interdependencies between the editing level and contextual characteristics of editing site. Results Here, we show that mRNA editing of individual nonsynonymous sites in cephalopods originates in evolution through substitutions at regions adjacent to these sites. As such substitutions mimic the effect of the substitution at the edited site itself, we hypothesize that they are favored by selection if the inosine is selectively advantageous to adenine at the edited position. Consistent with this hypothesis, we show that edited adenines are more frequently substituted with guanine, an informational analog of inosine, in the course of evolution than their unedited counterparts, and for heavily edited adenines, these transitions are favored by positive selection. Our study shows that coleoid editing sites may enhance adaptation, which, together with recent observations on Drosophila and human editing sites, points at a general role of RNA editing in the molecular evolution of metazoans.

scholarly journals Human C-to-U Coding RNA Editing Is Largely Nonadaptive

2018 ◽  
Vol 35 (4) ◽  
pp. 963-969 ◽  
Author(s):  
Zhen Liu ◽  
Jianzhi Zhang
Keyword(s):  
Rna Editing ◽  
Protein Function ◽  
Biological Significance ◽  
Rna Modification ◽  
Rna Molecules ◽  
Median Proportion ◽  
Specific Regulation ◽  
Time Specific ◽  
A Site ◽  
Editing Level

Abstract C-to-U RNA editing enzymatically converts the base C to U in RNA molecules and could lead to nonsynonymous changes when occurring in coding regions. Hundreds to thousands of coding sites were recently found to be C-to-U edited or editable in humans, but the biological significance of this phenomenon is elusive. Here, we test the prevailing hypothesis that nonsynonymous editing is beneficial because it provides a means for tissue- or time-specific regulation of protein function that may be hard to accomplish by mutations due to pleiotropy. The adaptive hypothesis predicts that the fraction of sites edited and the median proportion of RNA molecules edited (i.e., editing level) are both higher for nonsynonymous than synonymous editing. However, our empirical observations are opposite to these predictions. Furthermore, the frequency of nonsynonymous editing, relative to that of synonymous editing, declines as genes become functionally more important or evolutionarily more constrained, and the nonsynonymous editing level at a site is negatively correlated with the evolutionary conservation of the site. Together, these findings refute the adaptive hypothesis; they instead indicate that the reported C-to-U coding RNA editing is mostly slightly deleterious or neutral, probably resulting from off-target activities of editing enzymes. Along with similar conclusions on the more prevalent A-to-I editing and m6A modification of coding RNAs, our study suggests that, at least in humans, most events of each type of posttranscriptional coding RNA modification likely manifest cellular errors rather than adaptations, demanding a paradigm shift in the research of posttranscriptional modification.

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.

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 A-to-I RNA Editing in Cancer: From Evaluating the Editing Level to Exploring the Editing Effects

2021 ◽  
Vol 10 ◽  
Author(s):  
Heming Wang ◽  
Sinuo Chen ◽  
Jiayi Wei ◽  
Guangqi Song ◽  
Yicheng Zhao
Keyword(s):  
Rna Editing ◽  
Human Cancer ◽  
Parallel Optimization ◽  
Circular Rnas ◽  
Dna Mutation ◽  
Cellular Processes ◽  
Coding Regions ◽  
Bioinformatics Software ◽  
Amino Acid Mutations ◽  
Editing Level

As an important regulatory mechanism at the posttranscriptional level in metazoans, adenosine deaminase acting on RNA (ADAR)-induced A-to-I RNA editing modification of double-stranded RNA has been widely detected and reported. Editing may lead to non-synonymous amino acid mutations, RNA secondary structure alterations, pre-mRNA processing changes, and microRNA-mRNA redirection, thereby affecting multiple cellular processes and functions. In recent years, researchers have successfully developed several bioinformatics software tools and pipelines to identify RNA editing sites. However, there are still no widely accepted editing site standards due to the variety of parallel optimization and RNA high-seq protocols and programs. It is also challenging to identify RNA editing by normal protocols in tumor samples due to the high DNA mutation rate. Numerous RNA editing sites have been reported to be located in non-coding regions and can affect the biosynthesis of ncRNAs, including miRNAs and circular RNAs. Predicting the function of RNA editing sites located in non-coding regions and ncRNAs is significantly difficult. In this review, we aim to provide a better understanding of bioinformatics strategies for human cancer A-to-I RNA editing identification and briefly discuss recent advances in related areas, such as the oncogenic and tumor suppressive effects of RNA editing.

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