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https://www.readbyqxmd.com/read/28649357/rna-editing-by-the-host-adar-system-affects-the-molecular-evolution-of-the-zika-virus
#1
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
#2
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. In order to evaluate the ADAR2-FMRP interaction in mammals we analysed 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
#3
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
#4
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
#5
Liam P Keegan, Anzer Khan, Dragana Vukic, Mary A O'Connell
ADAR RNA editing enzymes (Adenosine Deaminases acting on RNA), that convert adenosine bases to inosines were first identified biochemically thirty 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...
May 30, 2017: RNA
https://www.readbyqxmd.com/read/28502110/a-novel-frameshift-mutation-of-the-adar1-gene-in-a-chinese-patient-with-dyschromatosis-symmetrica-hereditaria-and-the-dermoscopic-features
#6
LETTER
C Chi, Y Luo, J Liu
No abstract text is available yet for this article.
May 14, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28486975/evidence-for-transcriptome-wide-rna-editing-among-sus-scrofa-pre-1-sine-elements
#7
Scott A Funkhouser, Juan P Steibel, Ronald O Bates, Nancy E Raney, Darius Schenk, Catherine W Ernst
BACKGROUND: RNA editing by ADAR (adenosine deaminase acting on RNA) proteins is a form of transcriptional regulation that is widespread among humans and other primates. Based on high-throughput scans used to identify putative RNA editing sites, ADAR appears to catalyze a substantial number of adenosine to inosine transitions within repetitive regions of the primate transcriptome, thereby dramatically enhancing genetic variation beyond what is encoded in the genome. RESULTS: Here, we demonstrate the editing potential of the pig transcriptome by utilizing DNA and RNA sequence data from the same pig...
May 9, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28484266/rna-editing-signature-during-myeloid-leukemia-cell-differentiation
#8
C Rossetti, E Picardi, M Ye, G Camilli, A M D'Erchia, L Cucina, F Locatelli, L Fianchi, L Teofili, G Pesole, A Gallo, R Sorrentino
Adenosine deaminases acting on RNA (ADARs) are key proteins for hematopoietic stem cell self-renewal and for survival of differentiating progenitor cells. However, their specific role in myeloid cell maturation has been poorly investigated. Here we show that ADAR1 is present at basal level in the primary myeloid leukemia cells obtained from patients at diagnosis as well as in myeloid U-937 and THP1 cell lines and its expression correlates with the editing levels. Upon phorbol-myristate acetate or Vitamin D3/granulocyte macrophage colony-stimulating factor (GM-CSF)-driven differentiation, both ADAR1 and ADAR2 enzymes are upregulated, with a concomitant global increase of A-to-I RNA editing...
May 9, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28482199/adar-deaminase-a-to-i-editing-of-dna-and-rna-moieties-of-rna-dna-hybrids-has-implications-for-the-mechanism-of-ig-somatic-hypermutation
#9
Edward J Steele, Robyn A Lindley
The implications are discussed of recently published biochemical studies on ADAR-mediated A-to-I DNA and RNA deamination at RNA:DNA hybrids. The significance of these data are related to previous work on strand-biased and codon-context mutation signatures in B lymphocytes and cancer genomes. Those studies have established that there are two significant strand biases at A:T and G:C base pairs, A-site mutations exceed T-site mutations (A>T) by 2.9 fold and G-site mutations exceed C-site mutations (G>C) by 1...
April 21, 2017: DNA Repair
https://www.readbyqxmd.com/read/28455960/a-to-i-rna-editing-of-blcap-lost-the-inhibition-to-stat3-activation-in-cervical-cancer
#10
Wen Chen, Wenrong He, Hongbing Cai, Bicheng Hu, Caishang Zheng, Xianliang Ke, Li Xie, Zhenhua Zheng, Xinxing Wu, Hanzhong Wang
Bladder cancer-associated protein (BLCAP) gene is a highly conserved gene with tumor-suppressor function in different carcinomas. It is also a novel ADAR-mediated editing substrate undergoes multiple A-to-I RNA editing events. Although the anti-tumorigenic role of BLCAP has been examined in preliminarily studies, the relationship between BLCAP function and A-to-I RNA editing in cervical carcinogenesis still require further exploration. Herein, we analyzed the coding sequence of BLCAP transcripts in 35 paired cervical cancer samples using high-throughput sequencing...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28453786/a-to-i-rna-editing-in-the-earliest-diverging-eumetazoan-phyla
#11
Hagit T Porath, Amos Schaffer, Paulina Kaniewska, Shahar Alon, Eli Eisenberg, Joshua Rosenthal, Erez Y Levanon, Oren Levy
The highly conserved ADAR enzymes, found in all multicellular metazoans, catalyze the editing of mRNA transcripts by the deamination of adenosines to inosines. This type of editing has two general outcomes: site specific editing, which frequently leads to recoding, and clustered editing, which is usually found in transcribed genomic repeats. Here, for the first time we looked for both editing of isolated sites and clustered, non-specific sites in a basal metazoan, the coral Acropora millepora during spawning event, in order to reveal its editing pattern...
April 8, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28398248/adar1-and-microrna-a-hidden-crosstalk-in-cancer
#12
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
#13
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
#14
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
#15
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
#16
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...
May 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
#17
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
#18
REVIEW
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...
April 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
#19
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
#20
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
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