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https://www.readbyqxmd.com/read/28928239/the-rna-editing-enzyme-adar-promotes-lung-adenocarcinoma-migration-and-invasion-by-stabilizing-fak
#1
Elianna M Amin, Yuan Liu, Su Deng, Kay See Tan, Neel Chudgar, Marty W Mayo, Francisco Sanchez-Vega, Prasad S Adusumilli, Nikolaus Schultz, David R Jones
Large-scale, genome-wide studies report that RNA binding proteins are altered in cancers, but it is unclear how these proteins control tumor progression. We found that the RNA-editing protein ADAR (adenosine deaminase acting on double-stranded RNA) acted as a facilitator of lung adenocarcinoma (LUAD) progression through its ability to stabilize transcripts encoding focal adhesion kinase (FAK). In samples from 802 stage I LUAD patients, increased abundance of ADAR at both the mRNA and protein level correlated with tumor recurrence...
September 19, 2017: Science Signaling
https://www.readbyqxmd.com/read/28925356/the-c-elegans-neural-editome-reveals-an-adar-target-mrna-required-for-proper-chemotaxis
#2
Sarah N Deffit, Brian A Yee, Aidan C Manning, Suba Rajendren, Pranathi Vadlamani, Emily C Wheeler, Alain Domissy, Michael C Washburn, Gene W Yeo, Heather A Hundley
ADAR proteins alter gene expression both by catalyzing adenosine (A) to inosine (I) RNA editing and binding to regulatory elements in target RNAs. Loss of ADARs affects neuronal function in all animals studied to date. Caenorhabditis elegans lacking ADARs exhibit reduced chemotaxis, but the targets responsible for this phenotype remain unknown. To identify critical neural ADAR targets in C. elegans, we performed an unbiased assessment of the effects of ADR-2, the only A-to-I editing enzyme in C. elegans, on the neural transcriptome...
September 19, 2017: ELife
https://www.readbyqxmd.com/read/28924877/diagnostic-approach-to-neurotransmitter-monoamine-disorders-experience-from-clinical-biochemical-and-genetic-profiles
#3
Alice Kuster, Jean-Baptiste Arnoux, Magalie Barth, Delphine Lamireau, Nada Houcinat, Cyril Goizet, Bérénice Doray, Stéphanie Gobin, Manuel Schiff, Aline Cano, Daniel Amsallem, Christine Barnerias, Boris Chaumette, Marion Plaze, Abdelhamid Slama, Christine Ioos, Isabelle Desguerre, Anne-Sophie Lebre, Pascale de Lonlay, Laurence Christa
BACKGROUND AND AIM: To improve the diagnostic work-up of patients with diverse neurological diseases, we have elaborated specific clinical and CSF neurotransmitter patterns. METHODS: Neurotransmitter determinations in CSF from 1200 patients revealed abnormal values in 228 (19%) cases. In 54/228 (24%) patients, a final diagnosis was identified. RESULTS: We have reported primary (30/54, 56%) and secondary (24/54, 44%) monoamine neurotransmitter disorders...
September 18, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/28913566/adar-rna-editing-in-human-disease-more-to-it-than-meets-the-i
#4
REVIEW
Angela Gallo, Dragana Vukic, David Michalík, Mary A O'Connell, Liam P Keegan
We review the structures and functions of ADARs and their involvements in human diseases. ADAR1 is widely expressed, particularly in the myeloid component of the blood system, and plays a prominent role in promiscuous editing of long dsRNA. Missense mutations that change ADAR1 residues and reduce RNA editing activity cause Aicardi-Goutières Syndrome, a childhood encephalitis and interferonopathy that mimics viral infection and resembles an extreme form of Systemic Lupus Erythmatosus (SLE). In Adar1 mouse mutant models aberrant interferon expression is prevented by eliminating interferon activation signaling from cytoplasmic dsRNA sensors, indicating that unedited cytoplasmic dsRNA drives the immune induction...
September 14, 2017: Human Genetics
https://www.readbyqxmd.com/read/28874170/protein-recoding-by-adar1-mediated-rna-editing-is-not-essential-for-normal-development-and-homeostasis
#5
Jacki E Heraud-Farlow, Alistair M Chalk, Sandra E Linder, Qin Li, Scott Taylor, Joshua M White, Lokman Pang, Brian J Liddicoat, Ankita Gupte, Jin Billy Li, Carl R Walkley
BACKGROUND: Adenosine-to-inosine (A-to-I) editing of dsRNA by ADAR proteins is a pervasive epitranscriptome feature. Tens of thousands of A-to-I editing events are defined in the mouse, yet the functional impact of most is unknown. Editing causing protein recoding is the essential function of ADAR2, but an essential role for recoding by ADAR1 has not been demonstrated. ADAR1 has been proposed to have editing-dependent and editing-independent functions. The relative contribution of these in vivo has not been clearly defined...
September 5, 2017: Genome Biology
https://www.readbyqxmd.com/read/28856762/pregbalin-induced-recurrent-syncopal-attacks-with-prolong-qt-interval
#6
Adem Adar, Fahri Cakan, Orhan Önalan
Long QT syndrome may lead to fatal dysrhythmia. Prolongation of QT interval due to pregabalin has been shown in rats and no data is available in humans. We report a 80-year-old female patient using pregabalin. She was presented to emergency room with syncope attacks. Her admission electrocardiography demonstrated prolonged QT interval. After excluding the possible causes of the long QT syndrome, we attributed prolonged QT interval to pregabalin therapy. After discontinuation of pregabalin QT interval returned to normal range and patient experienced no further syncope attacks...
August 30, 2017: Annals of Noninvasive Electrocardiology
https://www.readbyqxmd.com/read/28837902/estimating-daily-minimum-maximum-and-mean-near-surface-air-temperature-using-hybrid-satellite-models-across-israel
#7
Adar Rosenfeld, Michael Dorman, Joel Schwartz, Victor Novack, Allan C Just, Itai Kloog
Meteorological stations measure air temperature (Ta) accurately with high temporal resolution, but usually suffer from limited spatial resolution due to their sparse distribution across rural, undeveloped or less populated areas. Remote sensing satellite-based measurements provide daily surface temperature (Ts) data in high spatial and temporal resolution and can improve the estimation of daily Ta. In this study we developed spatiotemporally resolved models which allow us to predict three daily parameters: Ta Max (day time), 24h mean, and Ta Min (night time) on a fine 1km grid across the state of Israel...
August 21, 2017: Environmental Research
https://www.readbyqxmd.com/read/28837675/the-interplay-between-maze-complexity-colony-size-learning-and-memory-in-ants-while-solving-a-maze-a-test-at-the-colony-level
#8
Maya Saar, Tomer Gilad, Tal Kilon-Kallner, Adar Rosenfeld, Aziz Subach, Inon Scharf
Central-place foragers need to explore their immediate habitat in order to reach food. We let colonies of the individually foraging desert ant Cataglyphis niger search for a food reward in a maze. We did so for three tests per day over two successive days and an additional test after a time interval of 4-20 days (seven tests in total). We examined whether the colonies reached the food reward faster, consumed more food and changed the number of workers searching over time, within and between days. Colonies' food-discovery time shortened within and between days, indicating that some workers learnt and became more efficient in moving through the maze...
2017: PloS One
https://www.readbyqxmd.com/read/28833649/adar1-splicing-mutation-leading-to-dyschromatosis-hereditaria-in-a-caucasian-patient
#9
J Petre, E Lasseaux, C Ged, B Arveiler, A Taïeb, F Morice-Picard
Dyschromatosis symmetrica hereditaria (DSH, OMIM 127400) is a rare autosomal dominant disorder characterized by hypo-and hyperpigmented macules on the dorsal aspects of hands and feet and freckle-like macules on the face(1). Histologically, there is an increase in epidermal melanin pigment in the hyperpigmented area and with normally structured melanosomes, together with an absence of melanin pigment in hypopigmented macules. The disease is known to be caused by mutations in the adenosine deaminase, RNA-specific (ADAR) gene (Miyamura et al...
August 21, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28820319/a-to-i-rna-editing-thinking-beyond-the-single-nucleotide
#10
Nabeel S Ganem, Ayelet T Lamm
Adenosine-to-inosine RNA editing is a conserved process, which is performed by ADAR enzymes. By changing nucleotides in coding regions of genes and altering codons, ADARs expand the cell's protein repertoire. This function of the ADAR enzymes is essential for human brain development. However, most of the known editing sites are in non-coding repetitive regions in the transcriptome and the purpose of editing in these regions is unclear. Recent studies, which have shown that editing levels of transcripts vary between tissues and developmental stages in many organisms, suggest that the targeted RNA and ADAR editing are both regulated...
August 18, 2017: RNA Biology
https://www.readbyqxmd.com/read/28798238/molecular-mechanisms-and-genomic-maps-of-dna-excision-repair-in-e-coli-and-humans
#11
Jinchuan Hu, Christopher P Selby, Sheera Adar, Ogun Adebali, Aziz Sancar
Nucleotide excision repair is a major DNA repair mechanism in all cellular organisms. In this repair system the DNA damage is removed by concerted dual incisions bracketing the damage and at precise distance from the damage. Here, we review the basic mechanisms of excision repair in E.coli and humans and the recent genome-wide mapping of DNA damage and repair in these organisms at single-nucleotide resolution.
August 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28762759/adenosine-to-inosine-rna-editing-in-health-and-disease
#12
Aikaterini Gatsiou, Nikolaos Vlachogiannis, Federica Francesca Lunella, Marco Sachse, Konstantinos Stellos
SIGNIFICANCE: Adenosine deaminase in transcriptome results in formation of inosine, a process that is called A-to-I RNA editing. Adenosine deaminase is one of the more than 140 described RNA modifications. A-to-I RNA editing is catalysed by the adenosine deaminases acting on RNA (ADAR) enzymes and is essential for life. Recent Advances: Accumulating evidence supports a critical role of RNA editing in all aspects of RNA metabolism including mRNA stability, splicing, nuclear export and localisation, as well as in recoding of proteins...
August 1, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28760719/ambient-coarse-particulate-matter-and-the-right-ventricle-the-multi-ethnic-study-of-atherosclerosis
#13
Jennifer C D'Souza, Steven M Kawut, Laura R Elkayam, Lianne Sheppard, Peter S Thorne, David R Jacobs, David A Bluemke, Joao A C Lima, Joel D Kaufman, Timothy V Larson, Sara D Adar
BACKGROUND: Coarse particulate matter (PM10-2.5) is primarily mechanically generated and includes crustal material, brake and tire wear, and biological particles. PM10-2.5 is associated with pulmonary disease, which can lead to right ventricular (RV) dysfunction. Although RV characteristics have been associated with combustion-related pollutants, relationships with PM10-2.5 remain unknown. OBJECTIVES: To quantify cross-sectional associations between RV dysfunction and PM10-2...
July 27, 2017: Environmental Health Perspectives
https://www.readbyqxmd.com/read/28746393/dynamic-hyper-editing-underlies-temperature-adaptation-in-drosophila
#14
Ilana Buchumenski, Osnat Bartok, Reut Ashwal-Fluss, Varun Pandey, Hagit T Porath, Erez Y Levanon, Sebastian Kadener
In Drosophila, A-to-I editing is prevalent in the brain, and mutations in the editing enzyme ADAR correlate with specific behavioral defects. Here we demonstrate a role for ADAR in behavioral temperature adaptation in Drosophila. Although there is a higher level of editing at lower temperatures, at 29°C more sites are edited. These sites are less evolutionarily conserved, more disperse, less likely to be involved in secondary structures, and more likely to be located in exons. Interestingly, hypomorph mutants for ADAR display a weaker transcriptional response to temperature changes than wild-type flies and a highly abnormal behavioral response upon temperature increase...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28716816/sphingosine-1-phosphate-receptor-1-promotes-environment-induced-and-acquired-chemoresistance
#15
Veronica Lifshitz, Saul J Priceman, Wenzhao Li, Gregory Cherryholmes, Heehyoung Lee, Adar Makovski-Silverstein, Lucia Borriello, Yves A DeClerck, Hua Yu
Drug resistance is a major barrier for the development of effective and durable cancer therapies. Overcoming this challenge requires further defining the cellular and molecular mechanisms underlying drug resistance, both acquired and environment-mediated drug resistance (EMDR). Here, using neuroblastoma (NB), a childhood cancer with high incidence of recurrence due to resistance to chemotherapy, as a model we show that human bone marrow-mesenchymal stromal cells induce tumor expression of sphingosine-1-phosphate receptor-1 (S1PR1) leading to their resistance to chemotherapy...
July 17, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28716651/significance-of-a-to-i-rna-editing-of-transcripts-modulating-pharmacokinetics-and-pharmacodynamics
#16
REVIEW
Masataka Nakano, Miki Nakajima
RNA editing is a post-transcriptional process that alters the nucleotide sequence of RNA transcripts to generate transcriptome diversity. Among the various types of RNA editing, adenosine-to-inosine (A-to-I) RNA editing is the most frequent type of RNA editing in mammals. Adenosine deaminases acting on RNA (ADAR) enzymes, ADAR1 and ADAR2, convert adenosines in double-stranded RNA structures into inosines by hydrolytic deamination. Inosine forms a base pair with cytidine as if it were guanosine; therefore, the conversion may affect the amino acid sequence, splicing, microRNA targeting, and miRNA maturation...
July 15, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28714361/rna-editing-is-induced-by-type-i-interferon-in-esophageal-squamous-cell-carcinoma
#17
Jinyao Zhang, Zhaoli Chen, Zefang Tang, Jianbing Huang, Xueda Hu, Jie He
In recent years, abnormal RNA editing has been shown to play an important role in the development of esophageal squamous cell carcinoma, as such abnormal editing is catalyzed by ADAR (adenosine deaminases acting on RNA). However, the regulatory mechanism of ADAR1 in esophageal squamous cell carcinomas remains largely unknown. In this study, we investigated ADAR1 expression and its association with RNA editing in esophageal squamous cell carcinomas. RNA sequencing applied to esophageal squamous cell carcinoma clinical samples showed that ADAR1 expression was correlated with the expression of STAT1, STAT2, and IRF9...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28710742/inpatient-weight-curve-trajectory-as-a-prognostic-factor-among-adolescents-with-anorexia-nervosa-a-preliminary-report
#18
Adar Avnon, Naomi Orkaby, Arik Hadas, Uri Berger, Anat Brunstein Klomek, Silvana Fennig
OBJECTIVE: To investigate the predictive value of weight restoration trajectories for relapse within the first year after discharge from inpatient treatment among adolescents with AN. METHODS: Forty four inpatient adolescents (5 boys, 39 girls) aged 11-18 (M 14.85, SD 1.87) diagnosed with anorexia were assessed at admission and discharge from a general hospital inpatient ward. Re-hospitalizations within 1 year of discharge were recorded. Factors assessed included 1/BMI at admission, 2/BMI at discharge, 3/percent from target weight (PFTW) at discharge, 4/length of hospitalization, and 5/a weight restoration trajectory measuring weight drops during inpatient weight restoration (rates of negative cubic variation in body weight (NCV)...
July 14, 2017: Eating and Weight Disorders: EWD
https://www.readbyqxmd.com/read/28649357/rna-editing-by-the-host-adar-system-affects-the-molecular-evolution-of-the-zika-virus
#19
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
#20
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. To evaluate the ADAR2-FMRP interaction in mammals we analyzed several RNA editing re-coding sites in the fmr1 knockout (KO) mice...
June 22, 2017: RNA Biology
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