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rna editing adar

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
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
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
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...
September 21, 2016: Nucleic Acids Research
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
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
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...
September 1, 2016: Nucleic Acids Research
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 UAG premature termination codon (PTC) to tryptophan (UGG) was improved from ∼11 % to ∼70 %...
August 23, 2016: Nucleic Acids Research
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...
August 17, 2016: RNA Biology
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
Victoria Marcu-Malina, Sanja Goldberg, Einav Vax, Ninette Amariglio, Itamar Goldstein, Gideon Rechavi
Adenosine deaminase acting on RNA (ADAR) 1 is the master editor of the transcriptome, catalyzing the conversion of adenosine to inosine (A-to-I). RNA transcripts fold into a variety of secondary structures including long intramolecular RNA duplexes that are the major substrate of ADAR1. Most A-to-I editing sites occur within RNA duplexes formed by complementary pairing of inverted retrotransposable elements interspersed within noncoding regions of transcripts. This catalytic activity of ADAR1 most likely prevents the abnormal activation of cytosolic nucleic acid sensors by self-dsRNAs...
August 2, 2016: Oncotarget
Wen Cai Zhang, Frank J Slack
Leukemic stem cells (LSCs) drive progression of chronic myeloid leukemia (CML) and tyrosine kinase inhibitor resistance through poorly understood mechanisms. Now in Cell Stem Cell, Zipeto et al. (2016) show targeting the RNA editing enzyme ADAR1 restores expression of let-7 and efficiently kills LSCs, providing an innovative therapeutic target in CML.
August 4, 2016: Cell Stem Cell
Yao Fu, Xingli Zhao, Zhaohui Li, Jun Wei, Yu Tian
The roles of alternative splicing and RNA editing in gene regulation and transcriptome diversity are well documented. Adenosine deaminases acting on RNA (ADARs) are responsible for adenosine-to-inosine (A-to-I) editing and exemplify the complex association between RNA editing and alternative splicing. The self-editing activity of ADAR2, which acts on its own pre-mRNA, leads to its alternative splicing. Alternative splicing occurs independently at nine splicing sites on ADAR2 pre-mRNA, generating numerous alternative splicing variants with various catalytic activities...
August 2016: Oncology Letters
Tim Hon Man Chan, Aditi Qamra, Kar Tong Tan, Jing Guo, Henry Yang, Lihua Qi, Jaymie Siqi Lin, Vanessa Hui En Ng, Yangyang Song, Huiqi Hong, Su Ting Tay, Yujing Liu, Jeeyun Lee, Sun Yong Rha, Feng Zhu, Jimmy Bok Yan So, Bin Tean Teh, Khay Guan Yeoh, Steve Rozen, Daniel G Tenen, Patrick Tan, Leilei Chen
BACKGROUD & AIMS: Gastric cancer (GC) is the third leading cause of global cancer mortality. Adenosine-to-inosine RNA editing is a recently described novel epigenetic mechanism involving sequence alterations at the RNA but not DNA level, primarily mediated by ADAR (adenosine deaminase that act on RNA) enzymes. Emerging evidence suggests a role for RNA editing and ADARs in cancer, however, the relationship between RNA editing and GC development and progression remains unknown. METHODS: In this study, we leveraged on the next-generation sequencing transcriptomics to demarcate the GC RNA editing landscape and the role of ADARs in this deadly malignancy...
October 2016: Gastroenterology
Brian J Liddicoat, Jochen C Hartner, Robert Piskol, Gokul Ramaswami, Alistair M Chalk, Paul D Kingsley, Vijay G Sankaran, Meaghan Wall, Louise E Purton, Peter H Seeburg, James Palis, Stuart H Orkin, Jun Lu, Jin Billy Li, Carl R Walkley
Adenosine deaminases that act on RNA (ADARs) convert adenosine residues to inosine in double-stranded RNA. In vivo, ADAR1 is essential for the maintenance of hematopoietic stem/progenitors. Whether other hematopoietic cell types also require ADAR1 has not been assessed. Using erythroid- and myeloid-restricted deletion of Adar1, we demonstrate that ADAR1 is dispensable for myelopoiesis but is essential for normal erythropoiesis. Adar1-deficient erythroid cells display a profound activation of innate immune signaling and high levels of cell death...
October 2016: Experimental Hematology
Shirley Oren Ben-Shoshan, Polina Kagan, Maya Sultan, Zohar Barabash, Chen Dor, Jasmine Jacob-Hirsch, Alon Harmelin, Orit Pappo, Victoria Marcu-Malina, Ziv Ben-Ari, Ninette Amariglio, Gideon Rechavi, Itamar Goldstein, Michal Safran
Adenosine deaminase acting on RNA (ADAR) 1 binds and edits double-stranded (ds) RNA secondary structures found mainly within untranslated regions of many transcripts. In the current research, our aim was to study the role of ADAR1 in liver homeostasis. As previous studies show a conserved immunoregulatory function for ADAR1 in mammalians, we focused on its role in preventing chronic hepatic inflammation and the associated activation of hepatic stellate cells to produce extracellular matrix and promote fibrosis...
June 30, 2016: RNA Biology
Taeyoung Hwang, Chul-Kee Park, Anthony K L Leung, Yuan Gao, Thomas M Hyde, Joel E Kleinman, Anandita Rajpurohit, Ran Tao, Joo Heon Shin, Daniel R Weinberger
RNA editing is increasingly recognized as a molecular mechanism regulating RNA activity and recoding proteins. Here we surveyed the global landscape of RNA editing in human brain tissues and identified three unique patterns of A-to-I RNA editing rates during cortical development: stable high, stable low and increasing. RNA secondary structure and the temporal expression of adenosine deaminase acting on RNA (ADAR) contribute to cis- and trans-regulatory mechanisms of these RNA editing patterns, respectively...
August 2016: Nature Neuroscience
Michael C Washburn, Heather A Hundley
RNA editing is a cellular process used to expand and diversify the RNA transcripts produced from a generally immutable genome. In animals, the most prevalent type of RNA editing is adenosine (A) to inosine (I) deamination catalyzed by the ADAR family. Throughout development, A-to-I editing levels increase while ADAR expression is constant, suggesting cellular mechanisms to regulate A-to-I editing exist. Furthermore, in several disease states, ADAR expression levels are similar to the normal state, but A-to-I editing levels are altered...
2016: Advances in Experimental Medicine and Biology
Matthew G Blango, Brenda L Bass
Endogenous double-stranded RNA (dsRNA) must be intricately regulated in mammals to prevent aberrant activation of host inflammatory pathways by cytosolic dsRNA binding proteins. Here, we define the long, endogenous dsRNA repertoire in mammalian macrophages and monocytes during the inflammatory response to bacterial lipopolysaccharide. Hyperediting by adenosine deaminases that act on RNA (ADAR) enzymes was quantified over time using RNA-seq data from activated mouse macrophages to identify 342 Editing Enriched Regions (EERs), indicative of highly structured dsRNA...
June 2016: Genome Research
Konstantin Licht, Utkarsh Kapoor, Elisa Mayrhofer, Michael F Jantsch
Alternative splicing and adenosine to inosine (A to I) RNA-editing are major factors leading to co- and post-transcriptional modification of genetic information. Both, A to I editing and splicing occur in the nucleus. As editing sites are frequently defined by exon-intron basepairing, mRNA splicing efficiency should affect editing levels. Moreover, splicing rates affect nuclear retention and will therefore also influence the exposure of pre-mRNAs to the editing-competent nuclear environment. Here, we systematically test the influence of splice rates on RNA-editing using reporter genes but also endogenous substrates...
July 27, 2016: Nucleic Acids Research
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