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https://www.readbyqxmd.com/read/28217931/how-do-adars-bind-rna-new-protein-rna-structures-illuminate-substrate-recognition-by-the-rna-editing-adars
#1
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
#2
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/28197591/predicting-brain-network-changes-in-alzheimer-s-disease-with-link-prediction-algorithms
#3
Sadegh Sulaimany, Mohammad Khansari, Peyman Zarrineh, Madelaine Daianu, Neda Jahanshad, Paul M Thompson, Ali Masoudi-Nejad
Link prediction is a promising research area for modeling various types of networks and has mainly focused on predicting missing links. Link prediction methods may be valuable for describing brain connectivity, as it changes in Alzheimer's disease (AD) and its precursor, mild cognitive impairment (MCI). Here, we analyzed 3-tesla whole-brain diffusion-weighted images from 202 participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) - 50 healthy controls, 72 with earlyMCI (eMCI) and 38 with lateMCI (lMCI) and 42 AD patients...
February 15, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28188287/a-to-i-rna-editing-up-regulates-human-dihydrofolate-reductase-in-breast-cancer
#4
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...
February 10, 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
#5
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
#6
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...
January 27, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28126736/rna-editing-enzyme-adar2-is-a-mediator-of-neuropathic-pain-after-peripheral-nerve-injury
#7
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
#8
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/28096334/role-of-cct-chaperonin-in-the-disassembly-of-mitotic-checkpoint-complexes
#9
Sharon Kaisari, Danielle Sitry-Shevah, Shirly Miniowitz-Shemtov, Adar Teichner, Avram Hershko
The mitotic checkpoint system prevents premature separation of sister chromatids in mitosis and thus ensures the fidelity of chromosome segregation. When this checkpoint is active, a mitotic checkpoint complex (MCC), composed of the checkpoint proteins Mad2, BubR1, Bub3, and Cdc20, is assembled. MCC inhibits the ubiquitin ligase anaphase promoting complex/cyclosome (APC/C), whose action is necessary for anaphase initiation. When the checkpoint signal is turned off, MCC is disassembled, a process required for exit from checkpoint-arrested state...
January 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28065306/measuring-abscission-spatiotemporal-dynamics-using-quantitative-high-resolution-microscopy
#10
O Gershony, S Sherman, S Adar, I Segal, D Nachmias, I Goliand, N Elia
The spatiotemporal characteristics of ESCRT (Endosomal Sorting Complex Required for Transport)-mediated mammalian cytokinetic abscission have been studied in recent years using quantitative high-resolution light microscopy techniques. Here we describe how to apply spinning disk live cell imaging and structured illumination microscopy (SIM) to define the dynamics and structural organization of abscission and of proteins involved in abscission in a quantitative manner. We further provide a protocol to correlate the structural data, obtained by SIM, to the dynamic information obtained by live cell recordings...
2017: Methods in Cell Biology
https://www.readbyqxmd.com/read/28059100/a-tailored-approach-to-braf-and-mlh1-methylation-testing-in-a-universal-screening-program-for-lynch-syndrome
#11
Tomer Adar, Linda H Rodgers, Kristen M Shannon, Makoto Yoshida, Tianle Ma, Anthony Mattia, Gregory Y Lauwers, Anthony J Iafrate, Daniel C Chung
To determine the correlation between BRAF genotype and MLH1 promoter methylation in a screening program for Lynch syndrome (LS), a universal screening program for LS was established in two medical centers. Tumors with abnormal MLH1 staining were evaluated for both BRAF V600E genotype and MLH1 promoter methylation. Tumors positive for both were considered sporadic, and genetic testing was recommended for all others. A total 1011 colorectal cancer cases were screened for Lynch syndrome, and 148 (14.6%) exhibited absent MLH1 immunostaining...
January 6, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28053121/adar2-regulates-rna-stability-by-modifying-access-of-decay-promoting-rna-binding-proteins
#12
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
#13
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/28046052/integrative-analysis-of-immunological-data-to-explore-chronic-immune-t-cell-activation-in-successfully-treated-hiv-patients
#14
Marie-Quitterie Picat, Isabelle Pellegrin, Juliette Bitard, Linda Wittkop, Cécile Proust-Lima, Benoît Liquet, Jean-François Moreau, Fabrice Bonnet, Patrick Blanco, Rodolphe Thiébaut
OBJECTIVES: To unravel the complex relationships between cytomegalovirus-induced-, autoimmune-induced responses, microbial translocation and chronic immune activation (CIA) in successfully treated HIV-infected patients and to explore the mediating role of alpha-interferon in these processes. DESIGN: Cross-sectional study nested in the ANRS CO3 Aquitaine Cohort, a prospective hospital-based cohort of HIV-1-infected patients in South-Western France. METHODS: Patients initiated antiretroviral therapy between 2005 and 2008 and were treated with sustained virological suppression for at least two years...
2017: PloS One
https://www.readbyqxmd.com/read/28035363/adar2-functions-as-a-tumor-suppressor-via-editing-igfbp7-in-esophageal-squamous-cell-carcinoma
#15
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
#16
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/28027584/il6-dependent-genomic-instability-heralds-accelerated-carcinogenesis-following-liver-regeneration-on-a-background-of-chronic-hepatitis
#17
Tali Lanton, Anat Shriki, Yael Nechemia-Arbely, Rinat Abramovitch, Orr Levkovitch, Revital Adar, Nofar Rosenberg, Mor Paldor, Daniel Goldenberg, Amir Sonnenblick, Amnon Peled, Stefan Rose-John, Eithan Galun, Jonathan H Axelrod
: Liver cancer, which typically develops on a background of chronic liver inflammation, is now the second leading cause of cancer mortality worldwide. For these patients surgical resection is a principal treatment modality that offers a chance of prolonged survival. However, tumor recurrence after resection, the mechanisms of which remain obscure, markedly limits the long-term survival of these patients. We have previously shown that partial hepatectomy (PH) in Mdr2 knockout (Mdr2(-/-) ) mice, a model of chronic inflammation-associated liver cancer, significantly accelerates hepatocarcinogenesis...
December 27, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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/27957596/the-biodegradable-spacer-as-a-novel-treatment-modality-for-massive-rotator-cuff-tears-a-prospective-study-with-5-year-follow-up
#19
Vladimir Senekovic, Boris Poberaj, Ladislav Kovacic, Martin Mikek, Eliyahu Adar, Elana Markovitz, Eran Maman, Assaf Dekel
BACKGROUND: The management of massive, irreparable rotator cuff tears (RCT) is challenging and associated with high failure rates. There are no current consensus or definitive guidelines concerning the optimal surgical treatment for this devastating condition. This study was designed to confirm the long-term safety and efficacy of the biodegradable inflatable InSpace™ system in patients with massive reparable or irreparable RCTs. METHODS: In this open-label, single arm, prospective study, subjects with massive RCT underwent subacromial implantation with the biodegradable spacer...
January 2017: Archives of Orthopaedic and Trauma Surgery
https://www.readbyqxmd.com/read/27937139/effects-of-aicardi-gouti%C3%A3-res-syndrome-mutations-predicted-from-adar-rna-structures
#20
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
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