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https://www.readbyqxmd.com/read/28398248/adar1-and-microrna-a-hidden-crosstalk-in-cancer
#1
REVIEW
Charles J Cho, Seung-Jae Myung, Suhwan Chang
The evolution of cancer cells is believed to be dependent on genetic or epigenetic alterations. However, this concept has recently been challenged by another mode of nucleotide alteration, RNA editing, which is frequently up-regulated in cancer. RNA editing is a biochemical process in which either Adenosine or Cytosine is deaminated by a group of RNA editing enzymes including ADAR (Adenosine deaminase; RNA specific) or APOBEC3B (Apolipoprotein B mRNA Editing Enzyme Catalytic Subunit 3B). The result of RNA editing is usually adenosine to inosine (A-to-I) or cytidine to uridine (C-to-U) transition, which can affect protein coding, RNA stability, splicing and microRNA-target interactions...
April 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28395340/testicular-adenosine-to-inosine-rna-editing-in-the-mouse-is-mediated-by-adarb1%C3%A2-%C3%A2
#2
Elizabeth M Snyder, Konstantin Licht, Robert E Braun
Adenosine to inosine (A-to-I) RNA editing occurs in a wide range of tissues and cell types and can be catalyzed by one of the two adenosine deaminase acting on double-stranded RNA enzymes, ADAR and ADARB1. Editing can impact both coding and noncoding regions of RNA, and in higher organisms has been proposed to function in adaptive evolution. Neither the prevalence of A-to-I editing nor the role of either ADAR or ADARB1 has been examined in the context of germ cell development in mammals. Computational analysis of whole testis and cell-type specific RNA-sequencing data followed by molecular confirmation demonstrated that A-to-I RNA editing occurs in both the germ line and in somatic Sertoli cells in two targets, Cog3 and Rpa1...
January 1, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28355180/dhx9-suppresses-rna-processing-defects-originating-from-the-alu-invasion-of-the-human-genome
#3
Tuğçe Aktaş, İbrahim Avşar Ilık, Daniel Maticzka, Vivek Bhardwaj, Cecilia Pessoa Rodrigues, Gerhard Mittler, Thomas Manke, Rolf Backofen, Asifa Akhtar
Transposable elements are viewed as 'selfish genetic elements', yet they contribute to gene regulation and genome evolution in diverse ways. More than half of the human genome consists of transposable elements. Alu elements belong to the short interspersed nuclear element (SINE) family of repetitive elements, and with over 1 million insertions they make up more than 10% of the human genome. Despite their abundance and the potential evolutionary advantages they confer, Alu elements can be mutagenic to the host as they can act as splice acceptors, inhibit translation of mRNAs and cause genomic instability...
April 6, 2017: Nature
https://www.readbyqxmd.com/read/28346055/a-to-i-editing-in-disease-is-not-fake-news
#4
Prajakta Bajad, Michael F Jantsch, Liam Keegan, Mary O'Connell
Adenosine deaminases acting on RNA (ADARs) are zinc-containing enzymes that deaminate adenosine bases to inosines within dsRNA regions in transcripts. In short, structured dsRNA hairpins individual adenosine bases may be targeted specifically and edited with up to one hundred percent efficiency, leading to the production of alternative protein variants. However, the majority of editing events occur within longer stretches of dsRNA formed by pairing of repetitive sequences. Here, many different adenosine bases are potential targets but editing efficiency is usually much lower...
March 27, 2017: RNA Biology
https://www.readbyqxmd.com/read/28278381/alternative-splicing-of-stat3-is-affected-by-rna-editing
#5
Lior Goldberg, Mor Abutbul-Amitai, Gideon Paret, Yael Nevo-Caspi
A-to-I RNA editing, carried out by adenosine deaminase acting on RNA (ADAR) enzymes, is an epigenetic phenomenon of posttranscriptional modifications on pre-mRNA. RNA editing in intronic sequences may influence alternative splicing of flanking exons. We have previously shown that conditions that induce editing result in elevated expression of signal transducer and activator of transcription 3 (STAT3), preferentially the alternatively-spliced STAT3β isoform. Mechanisms regulating alternative splicing of STAT3 have not been elucidated...
March 9, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28275585/mutational-pressure-in-zika-virus-local-adar-editing-areas-associated-with-pauses-in-translation-and-replication
#6
Vladislav V Khrustalev, Tatyana A Khrustaleva, Nitin Sharma, Rajanish Giri
Zika virus (ZIKV) spread led to the recent medical health emergency of international concern. Understanding the variations in virus system is of utmost need. Using available complete sequences of ZIKV we estimated directions of mutational pressure along the length of consensus sequences of three lineages of the virus. Results showed that guanine usage is growing in ZIKV RNA plus strand due to adenine to guanine transitions, while adenine usage is growing due to cytosine to adenine transversions. Especially high levels of guanine have been found in two-fold degenerated sites of certain areas of RNA plus strand with high amount of secondary structure...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28217931/how-do-adars-bind-rna-new-protein-rna-structures-illuminate-substrate-recognition-by-the-rna-editing-adars
#7
Justin M Thomas, Peter A Beal
Deamination of adenosine in RNA to form inosine has wide ranging consequences on RNA function including amino acid substitution to give proteins not encoded in the genome. What determines which adenosines in an mRNA are subject to this modification reaction? The answer lies in an understanding of the mechanism and substrate recognition properties of adenosine deaminases that act on RNA (ADARs). Our recent publication of X-ray crystal structures of the human ADAR2 deaminase domain bound to RNA editing substrates shed considerable light on how the catalytic domains of these enzymes bind RNA and promote adenosine deamination...
February 20, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28208661/differential-binding-of-three-major-human-adar-isoforms-to-coding-and-long-non-coding-transcripts
#8
Josephine Galipon, Rintaro Ishii, Yutaka Suzuki, Masaru Tomita, Kumiko Ui-Tei
RNA editing by deamination of adenosine to inosine is an evolutionarily conserved process involved in many cellular pathways, from alternative splicing to miRNA targeting. In humans, it is carried out by no less than three major adenosine deaminases acting on RNA (ADARs): ADAR1-p150, ADAR1-p110, and ADAR2. However, the first two derive from alternative splicing, so that it is currently impossible to delete ADAR1-p110 without also knocking out ADAR1-p150 expression. Furthermore, the expression levels of ADARs varies wildly among cell types, and no study has systematically explored the effect of each of these isoforms on the cell transcriptome...
February 11, 2017: Genes
https://www.readbyqxmd.com/read/28188287/a-to-i-rna-editing-up-regulates-human-dihydrofolate-reductase-in-breast-cancer
#9
Masataka Nakano, Tatsuki Fukami, Saki Gotoh, Miki Nakajima
Dihydrofolate reductase (DHFR) plays a key role in folate metabolism and is a target molecule of methotrexate. An increase in the cellular expression level of DHFR is one of the mechanisms of tumor resistance to methotrexate. The present study investigated the possibility that adenosine-to-inosine RNA editing, which causes nucleotide conversion by adenosine deaminase acting on RNA (ADAR) enzymes, might modulate DHFR expression. In human breast adenocarcinoma-derived MCF-7 cells, 26 RNA editing sites were identified in the 3'-UTR of DHFR...
March 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28148949/construction-of-a-guide-rna-for-site-directed-rna-mutagenesis-utilising-intracellular-a-to-i-rna-editing
#10
Masatora Fukuda, Hiromitsu Umeno, Kanako Nose, Azusa Nishitarumizu, Ryoma Noguchi, Hiroyuki Nakagawa
As an alternative to DNA mutagenesis, RNA mutagenesis can potentially become a powerful gene-regulation method for fundamental research and applied life sciences. Adenosine-to-inosine (A-to-I) RNA editing alters genetic information at the transcript level and is an important biological process that is commonly conserved in metazoans. Therefore, a versatile RNA-mutagenesis method can be achieved by utilising the intracellular RNA-editing mechanism. Here, we report novel guide RNAs capable of inducing A-to-I mutations by guiding the editing enzyme, human adenosine deaminase acting on RNA (ADAR)...
February 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28132026/dna-editing-in-dna-rna-hybrids-by-adenosine-deaminases-that-act-on-rna
#11
Yuxuan Zheng, Claire Lorenzo, Peter A Beal
Adenosine deaminases that act on RNA (ADARs) carry out adenosine (A) to inosine (I) editing reactions with a known requirement for duplex RNA. Here, we show that ADARs also react with DNA/RNA hybrid duplexes. Hybrid substrates are deaminated efficiently by ADAR deaminase domains at dA-C mismatches and with E to Q mutations in the base flipping loop of the enzyme. For a long, perfectly matched hybrid, deamination is more efficient with full length ADAR2 than its isolated deaminase domain. Guide RNA strands for directed DNA editing by ADAR were used to target six different 2΄-deoxyadenosines in the M13 bacteriophage ssDNA genome...
April 7, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28126736/rna-editing-enzyme-adar2-is-a-mediator-of-neuropathic-pain-after-peripheral-nerve-injury
#12
Hitoshi Uchida, Shinji Matsumura, Shunpei Okada, Tsutomu Suzuki, Toshiaki Minami, Seiji Ito
Transcriptional and post-translational regulations are important in peripheral nerve injury-induced neuropathic pain, but little is known about the role of post-transcriptional modification. Our objective was to determine the possible effect of adenosine deaminase acting on RNA (ADAR) enzymes, which catalyze post-transcriptional RNA editing, in tactile allodynia, a hallmark of neuropathic pain. Seven days after L5 spinal nerve transection (SNT) in adult mice, we found an increase in ADAR2 expression and a decrease in ADAR3 expression in the injured, but not in the uninjured, dorsal root ganglions (DRGs)...
January 26, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28106799/rna-editing-adar1-and-the-innate-immune-response
#13
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
#14
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...
April 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28049429/jacusa-site-specific-identification-of-rna-editing-events-from-replicate-sequencing-data
#15
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
#16
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
#17
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, mainly noncoding. Mutations in ADAR enzymes in Caenorhabditis 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, based on the observation that worms that lack both mechanisms do not exhibit defects, in contrast to the developmental defects observed when only RNA editing is absent...
March 2017: Genome Research
https://www.readbyqxmd.com/read/27999332/functions-of-the-rna-editing-enzyme-adar1-and-their-relevance-to-human-diseases
#18
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
#19
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...
February 2017: RNA Biology
https://www.readbyqxmd.com/read/27926534/irna-ai-identifying-the-adenosine-to-inosine-editing-sites-in-rna-sequences
#20
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
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