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rna editing adar

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https://www.readbyqxmd.com/read/29022589/dynamic-landscape-and-regulation-of-rna-editing-in-mammals
#1
Meng How Tan, Qin Li, Raghuvaran Shanmugam, Robert Piskol, Jennefer Kohler, Amy N Young, Kaiwen Ivy Liu, Rui Zhang, Gokul Ramaswami, Kentaro Ariyoshi, Ankita Gupte, Liam P Keegan, Cyril X George, Avinash Ramu, Ni Huang, Elizabeth A Pollina, Dena S Leeman, Alessandra Rustighi, Y P Sharon Goh, Ajay Chawla, Giannino Del Sal, Gary Peltz, Anne Brunet, Donald F Conrad, Charles E Samuel, Mary A O'Connell, Carl R Walkley, Kazuko Nishikura, Jin Billy Li
Adenosine-to-inosine (A-to-I) RNA editing is a conserved post-transcriptional mechanism mediated by ADAR enzymes that diversifies the transcriptome by altering selected nucleotides in RNA molecules. Although many editing sites have recently been discovered, the extent to which most sites are edited and how the editing is regulated in different biological contexts are not fully understood. Here we report dynamic spatiotemporal patterns and new regulators of RNA editing, discovered through an extensive profiling of A-to-I RNA editing in 8,551 human samples (representing 53 body sites from 552 individuals) from the Genotype-Tissue Expression (GTEx) project and in hundreds of other primate and mouse samples...
October 11, 2017: Nature
https://www.readbyqxmd.com/read/29017946/cloning-and-expression-of-malabar-grouper-epinephelus-malabaricus-adar1-gene-in-response-to-immune-stimulants-and-nervous-necrosis-virus
#2
Thirunavukkarasu Periyasamy, Joan Tang Xiao Joe, Ming-Wei Lu
ADARs are RNA editing catalysts that bind double-stranded RNA and convert adenosine to inosine, a process that can lead to destabilization of dsRNA structures and suppression of mRNA translation. In mammals, ADAR1 genes are involved in various cellular pathways, including interferon (IFN)-mediated response. However, the function of fish ADAR1 remains unclear. We report here the cloning of ADAR1 in Malabar grouper (Epinephelus malabaricus) (MgADAR1) and its response to various immune stimulants. The MgADAR1 cDNA is 5371-bp long, consisting of an open reading frame encoding a putative protein of 1381 amino acids, a 235-nt 5'-terminal untranslated region (UTR), and a 990-nt 3'-UTR...
October 7, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28985428/an-rna-editing-dsrna-binding-independent-gene-regulatory-mechanism-of-adars-and-its-clinical-implication-in-cancer
#3
Lihua Qi, Yangyang Song, Tim Hon Man Chan, Henry Yang, Chi Ho Lin, Daryl Jin Tai Tay, HuiQi Hong, Sze Jing Tang, Kar Tong Tan, Xi Xiao Huang, Jaymie Siqi Lin, Vanessa Hui En Ng, Julien Jean Pierre Maury, Daniel G Tenen, Leilei Chen
Adenosine-to-inosine (A-to-I) RNA editing, catalyzed by Adenosine DeAminases acting on double-stranded RNA(dsRNA) (ADAR), occurs predominantly in the 3΄ untranslated regions (3΄UTRs) of spliced mRNA. Here we uncover an unanticipated link between ADARs (ADAR1 and ADAR2) and the expression of target genes undergoing extensive 3΄UTR editing. Using METTL7A (Methyltransferase Like 7A), a novel tumor suppressor gene with multiple editing sites at its 3΄UTR, we demonstrate that its expression could be repressed by ADARs beyond their RNA editing and double-stranded RNA (dsRNA) binding functions...
July 29, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28974449/mechanisms-and-implications-of-adar-mediated-rna-editing-in-cancer
#4
Chen Wang, Jun Zou, Xiangyi Ma, Edward Wang, Guang Peng
Adenosine deaminases acting on RNA (ADARs) are enzymes that catalyze the conversion of adenosine (A) to inosine (I) in double-stranded RNAs. Inosine exhibits similar properties as guanosine. As a result, A-to-I editing has a great impact on edited RNAs, not only affecting the base pairing properties, but also altering codons after translation. A-to-I editing are known to mediate and diversify transcripts. However, the overall biological effect of ADARs are still largely unknown. Aberrant ADAR activity and editing dysregulation are present in a variety of cancers, including hepatocellular carcinoma, chronic myelogenous leukemia, glioblastoma and melanoma...
September 30, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28969707/massive-a-to-i-rna-editing-is-common-across-the-metazoa-and-correlates-with-dsrna-abundance
#5
Hagit T Porath, Binyamin A Knisbacher, Eli Eisenberg, Erez Y Levanon
BACKGROUND: Adenosine to inosine (A-to-I) RNA editing is a post-transcriptional modification catalyzed by the ADAR (adenosine deaminase that acts on RNA) enzymes, which are ubiquitously expressed among metazoans. Technical requirements have limited systematic mapping of editing sites to a small number of organisms. Thus, the extent of editing across the metazoan lineage is largely unknown. RESULTS: Here, we apply a computational procedure to search for RNA-sequencing reads containing clusters of editing sites in 21 diverse organisms...
October 2, 2017: Genome Biology
https://www.readbyqxmd.com/read/28968662/large-scale-prediction-of-adar-mediated-effective-human-a-to-i-rna-editing
#6
Li Yao, Heming Wang, Yuanyuan Song, Zhen Dai, Hao Yu, Ming Yin, Dongxu Wang, Xin Yang, Jinlin Wang, Tiedong Wang, Nan Cao, Jimin Zhu, Xizhong Shen, Guangqi Song, Yicheng Zhao
Adenosine-to-inosine (A-to-I) editing by adenosine deaminase acting on the RNA (ADAR) proteins is one of the most frequent modifications during post- and co-transcription. To facilitate the assignment of biological functions to specific editing sites, we designed an automatic online platform to annotate A-to-I RNA editing sites in pre-mRNA splicing signals, microRNAs (miRNAs) and miRNA target untranslated regions (3' UTRs) from human (Homo sapiens) high-throughput sequencing data and predict their effects based on large-scale bioinformatic analysis...
August 10, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/28928239/the-rna-editing-enzyme-adar-promotes-lung-adenocarcinoma-migration-and-invasion-by-stabilizing-fak
#7
Elianna M Amin, Yuan Liu, Su Deng, Kay See Tan, Neel Chudgar, Marty W Mayo, Francisco Sanchez-Vega, Prasad S Adusumilli, Nikolaus Schultz, David R Jones
Large-scale, genome-wide studies report that RNA binding proteins are altered in cancers, but it is unclear how these proteins control tumor progression. We found that the RNA-editing protein ADAR (adenosine deaminase acting on double-stranded RNA) acted as a facilitator of lung adenocarcinoma (LUAD) progression through its ability to stabilize transcripts encoding focal adhesion kinase (FAK). In samples from 802 stage I LUAD patients, increased abundance of ADAR at both the mRNA and protein level correlated with tumor recurrence...
September 19, 2017: Science Signaling
https://www.readbyqxmd.com/read/28925356/the-c-elegans-neural-editome-reveals-an-adar-target-mrna-required-for-proper-chemotaxis
#8
Sarah N Deffit, Brian A Yee, Aidan C Manning, Suba Rajendren, Pranathi Vadlamani, Emily C Wheeler, Alain Domissy, Michael C Washburn, Gene W Yeo, Heather A Hundley
ADAR proteins alter gene expression both by catalyzing adenosine (A) to inosine (I) RNA editing and binding to regulatory elements in target RNAs. Loss of ADARs affects neuronal function in all animals studied to date. Caenorhabditis elegans lacking ADARs exhibit reduced chemotaxis, but the targets responsible for this phenotype remain unknown. To identify critical neural ADAR targets in C. elegans, we performed an unbiased assessment of the effects of ADR-2, the only A-to-I editing enzyme in C. elegans, on the neural transcriptome...
September 19, 2017: ELife
https://www.readbyqxmd.com/read/28913566/adar-rna-editing-in-human-disease-more-to-it-than-meets-the-i
#9
REVIEW
Angela Gallo, Dragana Vukic, David Michalík, Mary A O'Connell, Liam P Keegan
We review the structures and functions of ADARs and their involvements in human diseases. ADAR1 is widely expressed, particularly in the myeloid component of the blood system, and plays a prominent role in promiscuous editing of long dsRNA. Missense mutations that change ADAR1 residues and reduce RNA editing activity cause Aicardi-Goutières Syndrome, a childhood encephalitis and interferonopathy that mimics viral infection and resembles an extreme form of Systemic Lupus Erythmatosus (SLE). In Adar1 mouse mutant models aberrant interferon expression is prevented by eliminating interferon activation signaling from cytoplasmic dsRNA sensors, indicating that unedited cytoplasmic dsRNA drives the immune induction...
September 14, 2017: Human Genetics
https://www.readbyqxmd.com/read/28874170/protein-recoding-by-adar1-mediated-rna-editing-is-not-essential-for-normal-development-and-homeostasis
#10
Jacki E Heraud-Farlow, Alistair M Chalk, Sandra E Linder, Qin Li, Scott Taylor, Joshua M White, Lokman Pang, Brian J Liddicoat, Ankita Gupte, Jin Billy Li, Carl R Walkley
BACKGROUND: Adenosine-to-inosine (A-to-I) editing of dsRNA by ADAR proteins is a pervasive epitranscriptome feature. Tens of thousands of A-to-I editing events are defined in the mouse, yet the functional impact of most is unknown. Editing causing protein recoding is the essential function of ADAR2, but an essential role for recoding by ADAR1 has not been demonstrated. ADAR1 has been proposed to have editing-dependent and editing-independent functions. The relative contribution of these in vivo has not been clearly defined...
September 5, 2017: Genome Biology
https://www.readbyqxmd.com/read/28820319/a-to-i-rna-editing-thinking-beyond-the-single-nucleotide
#11
Nabeel S Ganem, Ayelet T Lamm
Adenosine-to-inosine RNA editing is a conserved process, which is performed by ADAR enzymes. By changing nucleotides in coding regions of genes and altering codons, ADARs expand the cell's protein repertoire. This function of the ADAR enzymes is essential for human brain development. However, most of the known editing sites are in non-coding repetitive regions in the transcriptome and the purpose of editing in these regions is unclear. Recent studies, which have shown that editing levels of transcripts vary between tissues and developmental stages in many organisms, suggest that the targeted RNA and ADAR editing are both regulated...
August 18, 2017: RNA Biology
https://www.readbyqxmd.com/read/28762759/adenosine-to-inosine-rna-editing-in-health-and-disease
#12
Aikaterini Gatsiou, Nikolaos Vlachogiannis, Federica Francesca Lunella, Marco Sachse, Konstantinos Stellos
SIGNIFICANCE: Adenosine deamination in transcriptome results in the formation of inosine, a process that is called A-to-I RNA editing. Adenosine deamination is one of the more than 140 described RNA modifications. A-to-I RNA editing is catalyzed by adenosine deaminase acting on RNA (ADAR) enzymes and is essential for life. Recent Advances: Accumulating evidence supports a critical role of RNA editing in all aspects of RNA metabolism, including mRNA stability, splicing, nuclear export, and localization, as well as in recoding of proteins...
September 26, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28746393/dynamic-hyper-editing-underlies-temperature-adaptation-in-drosophila
#13
Ilana Buchumenski, Osnat Bartok, Reut Ashwal-Fluss, Varun Pandey, Hagit T Porath, Erez Y Levanon, Sebastian Kadener
In Drosophila, A-to-I editing is prevalent in the brain, and mutations in the editing enzyme ADAR correlate with specific behavioral defects. Here we demonstrate a role for ADAR in behavioral temperature adaptation in Drosophila. Although there is a higher level of editing at lower temperatures, at 29°C more sites are edited. These sites are less evolutionarily conserved, more disperse, less likely to be involved in secondary structures, and more likely to be located in exons. Interestingly, hypomorph mutants for ADAR display a weaker transcriptional response to temperature changes than wild-type flies and a highly abnormal behavioral response upon temperature increase...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28716651/significance-of-a-to-i-rna-editing-of-transcripts-modulating-pharmacokinetics-and-pharmacodynamics
#14
REVIEW
Masataka Nakano, Miki Nakajima
RNA editing is a post-transcriptional process that alters the nucleotide sequence of RNA transcripts to generate transcriptome diversity. Among the various types of RNA editing, adenosine-to-inosine (A-to-I) RNA editing is the most frequent type of RNA editing in mammals. Adenosine deaminases acting on RNA (ADAR) enzymes, ADAR1 and ADAR2, convert adenosines in double-stranded RNA structures into inosines by hydrolytic deamination. Inosine forms a base pair with cytidine as if it were guanosine; therefore, the conversion may affect the amino acid sequence, splicing, microRNA targeting, and miRNA maturation...
July 15, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28714361/rna-editing-is-induced-by-type-i-interferon-in-esophageal-squamous-cell-carcinoma
#15
Jinyao Zhang, Zhaoli Chen, Zefang Tang, Jianbing Huang, Xueda Hu, Jie He
In recent years, abnormal RNA editing has been shown to play an important role in the development of esophageal squamous cell carcinoma, as such abnormal editing is catalyzed by ADAR (adenosine deaminases acting on RNA). However, the regulatory mechanism of ADAR1 in esophageal squamous cell carcinomas remains largely unknown. In this study, we investigated ADAR1 expression and its association with RNA editing in esophageal squamous cell carcinomas. RNA sequencing applied to esophageal squamous cell carcinoma clinical samples showed that ADAR1 expression was correlated with the expression of STAT1, STAT2, and IRF9...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28649357/rna-editing-by-the-host-adar-system-affects-the-molecular-evolution-of-the-zika-virus
#16
Helen Piontkivska, Madeline Frederick, Michael M Miyamoto, Marta L Wayne
Zika virus (ZIKV) is a mosquito-transmitted flavivirus, linked to microcephaly and fetal death in humans. Here, we investigate whether host-mediated RNA editing of adenosines (ADAR) plays a role in the molecular evolution of ZIKV. Using complete coding sequences for the ZIKV polyprotein, we show that potential ADAR substitutions are underrepresented at the ADAR-resistant GA dinucleotides of both the positive and negative strands, that these changes are spatially and temporally clustered (as expected of ADAR editing) for three branches of the viral phylogeny, and that ADAR mutagenesis can be linked to its codon usage...
June 2017: Ecology and Evolution
https://www.readbyqxmd.com/read/28640668/absence-of-the-fragile-x-mental-retardation-protein-results-in-defects-of-rna-editing-of-neuronal-mrnas-in-mouse
#17
Alice Filippini, Daniela Bonini, Caroline Lacoux, Laura Pacini, Maria Zingariello, Laura Sancillo, Daniela Bosisio, Valentina Salvi, Jessica Mingardi, Luca La Via, Francesca Zalfa, Claudia Bagni, Alessandro Barbon
The fragile X syndrome (FXS), the most common form of inherited intellectual disability, is due to the absence of FMRP, a protein regulating RNA metabolism. Recently, an unexpected function of FMRP in modulating the activity of Adenosine Deaminase Acting on RNA (ADAR) enzymes has been reported both in Drosophila and Zebrafish. ADARs are RNA-binding proteins that increase transcriptional complexity through a post-transcriptional mechanism called RNA editing. To evaluate the ADAR2-FMRP interaction in mammals we analyzed several RNA editing re-coding sites in the fmr1 knockout (KO) mice...
June 22, 2017: RNA Biology
https://www.readbyqxmd.com/read/28640667/restricting-retrotransposons-adar1-is-another-guardian-of-the-human-genome
#18
Elisa Orecchini, Loredana Frassinelli, Alessandro Michienzi
ADAR1 is an enzyme that belongs to the Adenosine Deaminases Acting on RNA (ADARs) family. These enzymes deaminate adenosines to inosines (RNA editing A-to-I) within double-stranded RNA regions in transcripts. Since inosines are recognized as guanosines by the cellular machinery, RNA editing mediated by ADARs can either lead to the formation of an altered protein (recoding) or affect different aspects of RNA metabolism. Recently, a proteomic analysis led to the identification of novel ADAR1-associated factors and found that a good fraction of them is shared with the Long Interspersed Element 1 (LINE-1 or L1) ribonucleoparticles (RNPs)...
June 22, 2017: RNA Biology
https://www.readbyqxmd.com/read/28601223/adenosine-deaminases-that-act-on-rna-adars
#19
Yuru Wang, Yuxuan Zheng, Peter A Beal
Inosine is one of the most common modifications found in human RNAs and the Adenosine Deaminases that act on RNA (ADARs) are the main enzymes responsible for its production. ADARs were first discovered in the 1980s and since then our understanding of ADARs has advanced tremendously. For instance, it is now known that defective ADAR function can cause human diseases. Furthermore, recently solved crystal structures of the human ADAR2 deaminase bound to RNA have provided insights regarding the catalytic and substrate recognition mechanisms...
2017: Enzymes
https://www.readbyqxmd.com/read/28559490/adar-rna-editing-below-the-backbone
#20
REVIEW
Liam Keegan, Anzer Khan, Dragana Vukic, Mary O'Connell
ADAR RNA editing enzymes (adenosine deaminases acting on RNA) that convert adenosine bases to inosines were first identified biochemically 30 years ago. Since then, studies on ADARs in genetic model organisms, and evolutionary comparisons between them, continue to reveal a surprising range of pleiotropic biological effects of ADARs. This review focuses on Drosophila melanogaster, which has a single Adar gene encoding a homolog of vertebrate ADAR2 that site-specifically edits hundreds of transcripts to change individual codons in ion channel subunits and membrane and cytoskeletal proteins...
September 2017: RNA
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