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https://www.readbyqxmd.com/read/28106799/rna-editing-adar1-and-the-innate-immune-response
#1
REVIEW
Qingde Wang, Xiaoni Li, Ruofan Qi, Timothy Billiar
RNA editing, particularly A-to-I RNA editing, has been shown to play an essential role in mammalian embryonic development and tissue homeostasis, and is implicated in the pathogenesis of many diseases including skin pigmentation disorder, autoimmune and inflammatory tissue injury, neuron degeneration, and various malignancies. A-to-I RNA editing is carried out by a small group of enzymes, the adenosine deaminase acting on RNAs (ADARs). Only three members of this protein family, ADAR1-3, exist in mammalian cells...
January 18, 2017: Genes
https://www.readbyqxmd.com/read/28053121/adar2-regulates-rna-stability-by-modifying-access-of-decay-promoting-rna-binding-proteins
#2
Aparna Anantharaman, Vidisha Tripathi, Abid Khan, Je-Hyun Yoon, Deepak K Singh, Omid Gholamalamdari, Shuomeng Guang, Johan Ohlson, Helene Wahlstedt, Marie Öhman, Michael F Jantsch, Nicholas K Conrad, Jian Ma, Myriam Gorospe, Supriya G Prasanth, Kannanganattu V Prasanth
Adenosine deaminases acting on RNA (ADARs) catalyze the editing of adenosine residues to inosine (A-to-I) within RNA sequences, mostly in the introns and UTRs (un-translated regions). The significance of editing within non-coding regions of RNA is poorly understood. Here, we demonstrate that association of ADAR2 with RNA stabilizes a subset of transcripts. ADAR2 interacts with and edits the 3'UTR of nuclear-retained Cat2 transcribed nuclear RNA (Ctn RNA). In absence of ADAR2, the abundance and half-life of Ctn RNA are significantly reduced...
January 3, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28049429/jacusa-site-specific-identification-of-rna-editing-events-from-replicate-sequencing-data
#3
Michael Piechotta, Emanuel Wyler, Uwe Ohler, Markus Landthaler, Christoph Dieterich
BACKGROUND: RNA editing is a co-transcriptional modification that increases the molecular diversity, alters secondary structure and protein coding sequences by changing the sequence of transcripts. The most common RNA editing modification is the single base substitution (A→I) that is catalyzed by the members of the Adenosine deaminases that act on RNA (ADAR) family. Typically, editing sites are identified as RNA-DNA-differences (RDDs) in a comparison of genome and transcriptome data from next-generation sequencing experiments...
January 3, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28035363/adar2-functions-as-a-tumor-suppressor-via-editing-igfbp7-in-esophageal-squamous-cell-carcinoma
#4
Yuan-Bin Chen, Xiao-Yu Liao, Jiang-Bo Zhang, Fang Wang, Hai-De Qin, Lanjun Zhang, Yin Yao Shugart, Yi-Xin Zeng, Wei-Hua Jia
Esophageal squamous cell carcinoma (ESCC), one of the most aggressive cancers, is characterized by heterogeneous genetic and epigenetic changes. Recently, A-to-I RNA editing, catalyzed by adenosine deaminases acting on RNA (ADARs), was found to be aberrantly regulated during tumorigenesis. We previously reported that ADAR2 was downregulated in ESCC but its role was unclear. Thus, we report here that overexpression of ADAR2 can induce apoptosis in ESCC cell lines and inhibit tumor growth in vitro and in vivo...
February 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28031250/a-to-i-rna-editing-promotes-developmental-stage-specific-gene-and-lncrna-expression
#5
Boaz Goldstein, Lily Agranat-Tamir, Dean Light, Orna Ben-Naim Zgayer, Alla Fishman, Ayelet T Lamm
A-to-I RNA editing is a conserved widespread phenomenon in which adenosine (A) is converted to inosine (I) by adenosine deaminases (ADARs) in double-stranded RNA regions. Although human RNAs contain millions of A-to-I editing sites, most of these occur in noncoding regions and their function is unknown. Mutations in ADAR enzymes in C. elegans cause defects in normal development but are not lethal as in human and mouse. Previous studies in C. elegans indicated competition between RNA interference (RNAi) and RNA editing mechanisms, with the observation that worms that lack both mechanisms do not exhibit defects when only RNA editing is absent...
December 28, 2016: Genome Research
https://www.readbyqxmd.com/read/27999332/functions-of-the-rna-editing-enzyme-adar1-and-their-relevance-to-human-diseases
#6
REVIEW
Chunzi Song, Masayuki Sakurai, Yusuke Shiromoto, Kazuko Nishikura
Adenosine deaminases acting on RNA (ADARs) convert adenosine to inosine in double-stranded RNA (dsRNA). Among the three types of mammalian ADARs, ADAR1 has long been recognized as an essential enzyme for normal development. The interferon-inducible ADAR1p150 is involved in immune responses to both exogenous and endogenous triggers, whereas the functions of the constitutively expressed ADAR1p110 are variable. Recent findings that ADAR1 is involved in the recognition of self versus non-self dsRNA provide potential explanations for its links to hematopoiesis, type I interferonopathies, and viral infections...
December 17, 2016: Genes
https://www.readbyqxmd.com/read/27937139/effects-of-aicardi-gouti%C3%A3-res-syndrome-mutations-predicted-from-adar-rna-structures
#7
Andrew J Fisher, Peter A Beal
Adenosine (A) to inosine (I) RNA editing is important for life in metazoan organisms. Dysregulation or mutations that compromise the efficacy of A to I editing results in neurological disorders and a shorten life span. These reactions are catalyzed by adenosine deaminases acting on RNA (ADARs), which hydrolytically deaminate adenosines in regions of duplex RNA. Because inosine mimics guanosine in hydrogen bonding, this prolific RNA editing alters the sequence and structural information in the RNA landscape...
December 12, 2016: RNA Biology
https://www.readbyqxmd.com/read/27926534/irna-ai-identifying-the-adenosine-to-inosine-editing-sites-in-rna-sequences
#8
Wei Chen, Pengmian Feng, Hui Yang, Hui Ding, Hao Lin, Kuo-Chen Chou
Catalyzed by adenosine deaminase (ADAR), the adenosine to inosine (A-to-I) editing in RNA is not only involved in various important biological processes, but also closely associated with a series of major diseases. Therefore, knowledge about the A-to-I editing sites in RNA is crucially important for both basic research and drug development. Given an uncharacterized RNA sequence that contains many adenosine (A) residues, can we identify which one of them can be of A-to-I editing, and which one cannot? Unfortunately, so far no computational method whatsoever has been developed to address such an important problem based on the RNA sequence information alone...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27911851/inherited-variants-affecting-rna-editing-may-contribute-to-ovarian-cancer-susceptibility-results-from-a-large-scale-collaboration
#9
Jennifer B Permuth, Brett Reid, Madalene Earp, Y Ann Chen, Alvaro N A Monteiro, Zhihua Chen, Aocs Study Group, Georgia Chenevix-Trench, Peter A Fasching, Matthias W Beckmann, Diether Lambrechts, Adriaan Vanderstichele, Els Van Niewenhuyse, Ignace Vergote, Mary Anne Rossing, Jennifer Anne Doherty, Jenny Chang-Claude, Kirsten Moysich, Kunle Odunsi, Marc T Goodman, Yurii B Shvetsov, Lynne R Wilkens, Pamela J Thompson, Thilo Dörk, Natalia Bogdanova, Ralf Butzow, Heli Nevanlinna, Liisa Pelttari, Arto Leminen, Francesmary Modugno, Robert P Edwards, Roberta B Ness, Joseph Kelley, Florian Heitz, Beth Karlan, Jenny Lester, Susanne K Kjaer, Allan Jensen, Graham Giles, Michelle Hildebrandt, Dong Liang, Karen H Lu, Xifeng Wu, Douglas A Levine, Maria Bisogna, Andrew Berchuck, Daniel W Cramer, Kathryn L Terry, Shelley S Tworoger, Elizabeth M Poole, Elisa V Bandera, Brooke Fridley, Julie Cunningham, Stacey J Winham, Sara H Olson, Irene Orlow, Line Bjorge, Lambertus A Kiemeney, Leon Massuger, Tanja Pejovic, Melissa Moffitt, Nhu Le, Linda S Cook, Angela Brooks-Wilson, Linda E Kelemen, Jacek Gronwald, Jan Lubinski, Nicolas Wentzensen, Louise A Brinton, Jolanta Lissowska, Hanna Yang, Estrid Hogdall, Claus Hogdall, Lene Lundvall, Paul D P Pharoah, Honglin Song, Ian Campbell, Diana Eccles, Iain McNeish, Alice Whittemore, Valerie McGuire, Weiva Sieh, Joseph Rothstein, Catherine M Phelan, Harvey Risch, Steven Narod, John McLaughlin, Hoda Anton-Culver, Argyrios Ziogas, Usha Menon, Simon Gayther, Susan J Ramus, Aleksandra Gentry-Maharaj, Celeste Leigh Pearce, Anna H Wu, Jolanta Kupryjanczyk, Agnieszka Dansonka-Mieszkowska, Joellen M Schildkraut, Jin Q Cheng, Ellen L Goode, Thomas A Sellers
RNA editing in mammals is a form of post-transcriptional modification in which adenosine is converted to inosine by the adenosine deaminases acting on RNA (ADAR) family of enzymes. Based on evidence of altered ADAR expression in epithelial ovarian cancers (EOC), we hypothesized that single nucleotide polymorphisms (SNPs) in ADAR genes modify EOC susceptibility, potentially by altering ovarian tissue gene expression. Using directly genotyped and imputed data from 10,891 invasive EOC cases and 21,693 controls, we evaluated the associations of 5,303 SNPs in ADAD1, ADAR, ADAR2, ADAR3, and SND1...
July 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27797325/-adar-mediated-messenger-rna-editing-analysis-at-the-proteome-level
#10
REVIEW
A A Kliuchnikova, K G Kuznetsova, S A Moshkovskii
Post-transcriptional RNA editing by RNA specific adenosine deaminases (ADAR) was discovered more than two decades ago. It provides additional regulation of animal and human transcriptome. In most cases, it occurs in nervous tissue, where, as a result of the reaction, adenosine is converted to inosine in particular sites of RNA. In case of messenger RNA, during translation, inosine is recognized as guanine leading to amino acid substitutions. Those substitutions are shown to affect substantially the function of proteins, e...
July 2016: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://www.readbyqxmd.com/read/27696924/the-rna-editing-deaminase-adar-is-involved-in-stress-resistance-of-artemia-diapause-embryos
#11
Li Dai, Xue-Chen Liu, Sen Ye, Hua-Wei Li, Dian-Fu Chen, Xiao-Jian Yu, Xue-Ting Huang, Li Zhang, Fan Yang, Jin-Shu Yang, Wei-Jun Yang
The most widespread type of RNA editing, conversion of adenosine to inosine (A→I), is catalyzed by two members of the adenosine deaminase acting on RNA (ADAR) family, ADAR1 and ADAR2. These enzymes edit transcripts for neurotransmitter receptors and ion channels during adaption to changes in the physical environment. In the primitive crustacean Artemia, when maternal adults are exposed to unfavorable conditions, they release diapause embryos to withstand harsh environments. The aim of the current study was therefore to elucidate the role of ADAR of Artemia diapause embryos in resistance to stress...
October 4, 2016: Stress: the International Journal on the Biology of Stress
https://www.readbyqxmd.com/read/27695712/rna-editing-dynamically-rewrites-the-cancer-code
#12
COMMENT
Violeta Rayon-Estrada, F Nina Papavasiliou, Dewi Harjanto
Global analyses of cancer transcriptomes demonstrate that ADAR (adenosine deaminase, RNA-specific)-mediated RNA editing dynamically contributes to genetic alterations in cancer, and directly correlates with progression and prognosis. RNA editing is abundant and frequently elevated in cancer, and affects functionally and clinically relevant sites in both coding and non-coding regions of the transcriptome. Therefore, ADAR and differentially edited transcripts may be promising biomarkers or targets for therapy...
December 2015: Trends in Cancer
https://www.readbyqxmd.com/read/27687780/single-cell-rna-sequencing-reveals-dynamic-changes-in-a-to-i-rna-editome-during-early-human-embryogenesis
#13
Si Qiu, Wenhui Li, Heng Xiong, Dongbing Liu, Yali Bai, Kui Wu, Xiuqing Zhang, Huanming Yang, Kun Ma, Yong Hou, Bo Li
BACKGROUND: A-to-I RNA-editing mediated by ADAR (adenosine deaminase acting on RNA) enzymes that converts adenosine to inosine in RNA sequence can generate mutations and alter gene regulation in metazoans. Previous studies have shown that A-to-I RNA-editing plays vital roles in mouse embryogenesis. However, the RNA-editing activities in early human embryonic development have not been investigated. RESULTS: Here, we characterized genome-wide A-to-I RNA-editing activities during human early embryogenesis by profiling 68 single cells from 29 human embryos spanning from oocyte to morula stages...
September 29, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27658966/adar1-restricts-line-1-retrotransposition
#14
Elisa Orecchini, Margherita Doria, Ambra Antonioni, Silvia Galardi, Silvia Anna Ciafrè, Loredana Frassinelli, Carmine Mancone, Claudia Montaldo, Marco Tripodi, Alessandro Michienzi
Adenosine deaminases acting on RNA (ADARs) are involved in RNA editing that converts adenosines to inosines in double-stranded RNAs. ADAR1 was demonstrated to be functional on different viruses exerting either antiviral or proviral effects. Concerning HIV-1, several studies showed that ADAR1 favors viral replication. The aim of this study was to investigate the composition of the ADAR1 ribonucleoprotein complex during HIV-1 expression. By using a dual-tag affinity purification procedure in cells expressing HIV-1 followed by mass spectrometry analysis, we identified 14 non-ribosomal ADAR1-interacting proteins, most of which are novel...
January 9, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/27614234/role-of-host-driven-mutagenesis-in-determining-genome-evolution-of-sigma-virus-dmelsv-rhabdoviridae-in-drosophila-melanogaster
#15
Helen Piontkivska, Luis F Matos, Sinu Paul, Brian Scharfenberg, William G Farmerie, Michael M Miyamoto, Marta L Wayne
Sigma virus (DMelSV) is ubiquitous in natural populations of Drosophila melanogaster. Host-mediated, selective RNA editing of adenosines to inosines (ADAR) may contribute to control of viral infection by preventing transcripts from being transported into the cytoplasm or being translated accurately; or by increasing the viral genomic mutation rate. Previous PCR-based studies showed that ADAR mutations occur in DMelSV at low frequency. Here we use SOLiD(TM) deep sequencing of flies from a single host population from Athens, GA, USA to comprehensively evaluate patterns of sequence variation in DMelSV with respect to ADAR...
October 5, 2016: Genome Biology and Evolution
https://www.readbyqxmd.com/read/27595325/adenosine-to-inosine-rna-editing-controls-cathepsin-s-expression-in-atherosclerosis-by-enabling-hur-mediated-post-transcriptional-regulation
#16
Konstantinos Stellos, Aikaterini Gatsiou, Kimon Stamatelopoulos, Ljubica Perisic Matic, David John, Federica Francesca Lunella, Nicolas Jaé, Oliver Rossbach, Carolin Amrhein, Frangiska Sigala, Reinier A Boon, Boris Fürtig, Yosif Manavski, Xintian You, Shizuka Uchida, Till Keller, Jes-Niels Boeckel, Anders Franco-Cereceda, Lars Maegdefessel, Wei Chen, Harald Schwalbe, Albrecht Bindereif, Per Eriksson, Ulf Hedin, Andreas M Zeiher, Stefanie Dimmeler
Adenosine-to-inosine (A-to-I) RNA editing, which is catalyzed by a family of adenosine deaminase acting on RNA (ADAR) enzymes, is important in the epitranscriptomic regulation of RNA metabolism. However, the role of A-to-I RNA editing in vascular disease is unknown. Here we show that cathepsin S mRNA (CTSS), which encodes a cysteine protease associated with angiogenesis and atherosclerosis, is highly edited in human endothelial cells. The 3' untranslated region (3' UTR) of the CTSS transcript contains two inverted repeats, the AluJo and AluSx(+) regions, which form a long stem-loop structure that is recognized by ADAR1 as a substrate for editing...
October 2016: Nature Medicine
https://www.readbyqxmd.com/read/27587585/rediportal-a-comprehensive-database-of-a-to-i-rna-editing-events-in-humans
#17
Ernesto Picardi, Anna Maria D'Erchia, Claudio Lo Giudice, Graziano Pesole
RNA editing by A-to-I deamination is the prominent co-/post-transcriptional modification in humans. It is carried out by ADAR enzymes and contributes to both transcriptomic and proteomic expansion. RNA editing has pivotal cellular effects and its deregulation has been linked to a variety of human disorders including neurological and neurodegenerative diseases and cancer. Despite its biological relevance, many physiological and functional aspects of RNA editing are yet elusive. Here, we present REDIportal, available online at http://srv00...
January 4, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/27557710/an-efficient-system-for-selectively-altering-genetic-information-within-mrnas
#18
Maria Fernanda Montiel-González, Isabel C Vallecillo-Viejo, Joshua J C Rosenthal
Site-directed RNA editing (SDRE) is a strategy to precisely alter genetic information within mRNAs. By linking the catalytic domain of the RNA editing enzyme ADAR to an antisense guide RNA, specific adenosines can be converted to inosines, biological mimics for guanosine. Previously, we showed that a genetically encoded iteration of SDRE could target adenosines expressed in human cells, but not efficiently. Here we developed a reporter assay to quantify editing, and used it to improve our strategy. By enhancing the linkage between ADAR's catalytic domain and the guide RNA, and by introducing a mutation in the catalytic domain, the efficiency of converting a U A: G premature termination codon (PTC) to tryptophan (U G: G) was improved from ∼11 % to ∼70 %...
December 1, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27533598/a-to-i-rna-editing-independent-of-adars-in-filamentous-fungi
#19
Chenfang Wang, Jin-Rong Xu, Huiquan Liu
ADAR mediated A-to-I RNA editing is thought to be unique to animals and occurs mainly in the non-coding regions. Recently filamentous fungi such as Fusarium graminearum were found to lack orthologs of animal ADARs but have stage-specific A-to-I editing during sexual reproduction. Unlike animals, majority of editing sites are in the coding regions and often result in missense and stop loss changes in fungi. Furthermore, whereas As in RNA stems are targeted by animal ADARs, RNA editing in fungi preferentially targets As in hairpin loops, implying that fungal RNA editing involves mechanisms related to editing of the anticodon loop by ADATs...
October 2, 2016: RNA Biology
https://www.readbyqxmd.com/read/27514783/functional-characterizations-and-expression-profiles-of-adar2-gene-responsible-for-rna-editing-in-response-to-gcrv-challenge-in-grass-carp-ctenopharyngodon-idella
#20
Juanjuan Su, Baoquan Han, Youliang Rao, Xiaoli Feng, Jianguo Su
ADAR (adenosine deaminases acting on RNA)-mediated adenosine-to-inosine (A-to-I) editing to double-stranded RNA (dsRNA) is a critical arm of the antiviral response. The present study focused on the structural and functional characterizations of grass carp (Ctenopharyngodon idella) ADAR2 (CiADAR2) gene. The complete genomic sequence of CiADAR2 is 150,458 bp in length, containing 12 exons and 11 introns. The open reading frame (ORF) of 2100 bp encodes a polypeptide of 699 amino acids (aa) which contains three highly conservative domains - two N-terminal dsRNA binding domains (dsRBDs) and one C-terminal deaminase domain...
September 2016: Fish & Shellfish Immunology
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