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https://www.readbyqxmd.com/read/28436945/adar1-controls-apoptosis-of-stressed-cells-by-inhibiting-staufen1-mediated-mrna-decay
#1
Masayuki Sakurai, Yusuke Shiromoto, Hiromitsu Ota, Chunzi Song, Andrew V Kossenkov, Jayamanna Wickramasinghe, Louise C Showe, Emmanuel Skordalakes, Hsin-Yao Tang, David W Speicher, Kazuko Nishikura
Both p150 and p110 isoforms of ADAR1 convert adenosine to inosine in double-stranded RNA (dsRNA). ADAR1p150 suppresses the dsRNA-sensing mechanism that activates MDA5-MAVS-IFN signaling in the cytoplasm. In contrast, the biological function of the ADAR1p110 isoform, which is usually located in the nucleus, is largely unknown. Here, we show that stress-activated phosphorylation of ADAR1p110 by MKK6-p38-MSK MAP kinases promotes its binding to Exportin-5 and its export from the nucleus. After translocating to the cytoplasm, ADAR1p110 suppresses apoptosis in stressed cells by protecting many antiapoptotic gene transcripts that contain 3'-untranslated-region dsRNA structures primarily comprising inverted Alu repeats...
April 24, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28411194/systematic-characterization-of-a-to-i-rna-editing-hotspots-in-micrornas-across-human-cancers
#2
Yumeng Wang, Xiaoyan Xu, Shuangxing Yu, Kang Jin Kang, Zhicheng Zhou, Leng Han, Yiu Huen Tsang, Jun Li, Hu Chen, Lingegowda S Mangala, Yuan Yuan, A Karina Eterovic, Yiling Lu, Anil K Sood, Kenneth L Scott, Gordon B Mills, Han Liang
RNA editing, a widespread posttranscriptional mechanism, has emerged as a new player in cancer biology. Recent studies have reported key roles for individual miRNA editing events, but a comprehensive picture of miRNA editing in human cancers remains largely unexplored. Here we systematically characterized the miRNA editing profiles of 8,595 samples across 20 cancer types from miRNA sequencing data of The Cancer Genome Atlas and identified 19 adenosine-to-inosine (A-to-I) RNA editing hotspots. We independently validated 15 of them by perturbation experiments in several cancer cell lines...
April 14, 2017: Genome Research
https://www.readbyqxmd.com/read/28398248/adar1-and-microrna-a-hidden-crosstalk-in-cancer
#3
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
#4
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/28393624/favored-and-less-favored-codon-anticodon-duplexes-arising-from-the-gc-codon-family-box-encoding-for-alanine-some-computational-perspectives
#5
Martina Devi, R H Duncan Lyngdoh
Alanine is encoded by the four codons of the GC box (GCA, GCG, GCU, and GCC). Known alanine anticodons include the UGC, IGC, and VGC triplets (I = inosine; V = uridine-5-oxyacetic acid). The energy-minimized structures of all possible codon-anticodon combinations involving all the alanine codons GCA, GCG, GCU, and GCC with the alanine anticodons UGC, IGC, and VGC are studied using the AMBER software. Fifteen H-bonded duplex structures arising out of these combinations are studied here, all having Watson-Crick-type base pairs at the first and second codon positions, and a variety of base pairing possibilities at the third (or wobble) position...
April 10, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28392841/assessing-alternative-base-substitutions-at-primer-cpg-sites-to-optimise-unbiased-pcr-amplification-of-methylated-sequences
#6
Ida L M Candiloro, Thomas Mikeska, Alexander Dobrovic
BACKGROUND: Determining the role of DNA methylation in various biological processes is dependent on the accurate representation of often highly complex patterns. Accurate representation is dependent on unbiased PCR amplification post bisulfite modification, regardless of methylation status of any given epiallele. This is highly dependent on primer design. Particular difficulties are raised by the analysis of CpG-rich regions, which are the usual regions of interest. Here, it is often difficult or impossible to avoid placing primers in CpG-free regions, particularly if one wants to target a specific part of a CpG-rich region...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28391009/the-promise-of-pharmacogenomics-in-reducing-toxicity-during-acute-lymphoblastic-leukemia-maintenance-treatment
#7
REVIEW
Shoshana Rudin, Marcus Marable, R Stephanie Huang
Pediatric acute lymphoblastic leukemia (ALL) affects a substantial number of children every year and requires a long and rigorous course of chemotherapy treatments in three stages, with the longest phase, the maintenance phase, lasting 2-3years. While the primary drugs used in the maintenance phase, 6-mercaptopurine (6-MP) and methotrexate (MTX), are necessary for decreasing risk of relapse, they also have potentially serious toxicities, including myelosuppression, which may be life-threatening, and gastrointestinal toxicity...
April 6, 2017: Genomics, Proteomics & Bioinformatics
https://www.readbyqxmd.com/read/28389646/high-expression-of-impdh2-is-associated-with-aggressive-features-and-poor-prognosis-of-primary-nasopharyngeal-carcinoma
#8
Yi Xu, Zhousan Zheng, Ying Gao, Shiyu Duan, Cui Chen, Jian Rong, Kebing Wang, Miao Yun, Huiwen Weng, Sheng Ye, Jiaxing Zhang
Inosine monophosphate dehydrogenase type II (IMPDH2) has been shown to play critical roles in the development and progression of several human cancers. However, little is known about IMPDH2 expression and its clinical significance in nasopharyngeal carcinoma (NPC). Western blotting, qRT-PCR and immunohistochemistry were employed to evaluate IMPDH2 expression in NPC cell lines and tissues. In our study, elevated expression of IMPDH2 was observed at both the protein and mRNA levels in NPC cell lines than in NPEC2 Bmi-1...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28382976/three-serum-metabolite-signatures-for-diagnosing-low-grade-and-high-grade-bladder-cancer
#9
Guangguo Tan, Haibo Wang, Jianlin Yuan, Weijun Qin, Xin Dong, Hong Wu, Ping Meng
To address the shortcomings of cystoscopy and urine cytology for detecting and grading bladder cancer (BC), ultrahigh performance liquid chromatography (UHPLC) coupled with Q-TOF mass spectrometry in conjunction with univariate and multivariate statistical analyses was employed as an alternative method for the diagnosis of BC. A series of differential serum metabolites were further identified for low-grade(LG) and high-grade(HG) BC patients, suggesting metabolic dysfunction in malignant proliferation, immune escape, differentiation, apoptosis and invasion of cancer cells in BC patients...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28359946/use-of-in%C3%A2-vivo-induced-technology-to-identify-antigens-expressed-by-photobacterium-damselae-subsp-piscicida-during-infection-of-senegalese-sole-solea-senegalensis
#10
J A Núñez-Díaz, M Fumanal, E Viguera, M A Moriñigo, M C Balebona
Photobacterium damselae subsp. piscicida (Phdp), the causative agent of photobacteriosis, is an important pathogen in marine aquaculture that affects many different fish species worldwide, including Solea senegalensis, an important fish species for aquaculture in the south of Europe. Bacteria express different repertoires of proteins in response to environmental conditions and when invading a host, sense in vivo environment and adapt by changing the expression of specific proteins. In the case of pathogens, identification of genes with up-regulated expression in vivo compared to in vitro conditions might give an insight into the genes relevant to the bacterial virulence...
May 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28346055/a-to-i-editing-in-disease-is-not-fake-news
#11
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/28345353/a-combined-approach-to-decrease-the-technological-and-sensory-defects-caused-by-fat-and-sodium-reduction-in-bologna-type-sausages
#12
Paulo Cezar Bastianello Campagnol, Bibiana Alves Dos Santos, José Manuel Lorenzo, Alexandre José Cichoski
The effect of the addition of fructooligosaccharides, transglutaminase, disodium inosinate, and disodium guanylate on some technological and sensory parameters of low-fat and low-salt Bologna-type sausages was evaluated. In the first experiment, sausages with a 25% and 50% fat reduction containing 0, 3%, or 6% fructooligosaccharides were manufactured. Fat reduction adversely affected the emulsion stability, hardness, and sensory properties; however, the addition of 6% fructooligosaccharides reduced the loss of quality associated with a lower fat content...
January 1, 2017: Food Science and Technology International, Ciencia y Tecnología de Los Alimentos Internacional
https://www.readbyqxmd.com/read/28343345/assessment-of-nucleosides-as-putative-tumor-biomarkers-in-prostate-cancer-screening-by-ce-uv
#13
Adriana Zardini Buzatto, Mariana de Oliveira Silva, Ronei Jesus Poppi, Ana Valéria Colnaghi Simionato
Cancer is responsible for millions of deaths worldwide, but most base diseases may be cured if detected early. Screening tests may be used to identify early-stage malignant neoplasms. However, the major screening tool for prostate cancer, the prostate-specific antigen test, has unsuitable sensitivity. Since cancer cells may affect the pattern of consumption and excretion of nucleosides, such biomolecules are putative biomarkers that can be used for diagnosis and treatment evaluation. Using a previously validated method for the analysis of nucleosides in blood serum by capillary electrophoresis with UV-vis spectroscopy detection, we investigated 60 samples from healthy individuals and 42 samples from prostate cancer patients...
March 25, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28339176/identification-of-likely-associations-between-cerebral-folate-deficiency-and-complex-genetic-and-metabolic-pathogenesis-of-autism-spectrum-disorders-by-utilization-of-a-pilot-interaction-modeling-approach
#14
Daniel Krsička, Jan Geryk, Markéta Vlčková, Markéta Havlovicová, Milan Macek, Radka Pourová
Recently, cerebral folate deficiency (CFD) was suggested to be involved in the pathogenesis of autism spectrum disorders (ASD). However, the exact role of folate metabolism in the pathogenesis of ASD, identification of underlying pathogenic mechanisms and impaired metabolic pathways remain unexplained. The aim of our study was to develop and test a novel, unbiased, bioinformatics approach in order to identify links between ASD and disturbed cerebral metabolism by focusing on abnormal folate metabolism, which could foster patient stratification and novel therapeutic interventions...
March 24, 2017: Autism Research: Official Journal of the International Society for Autism Research
https://www.readbyqxmd.com/read/28339063/viral-and-host-factors-associated-with-outcomes-of-hepatitis-c-virus-infection-review
#15
Zehui Yan, Yuming Wang
Hepatitis C virus (HCV) infection is a major health issue globally. Owing to the progress made in host genetics and HCV molecular virology, emerging data have suggested that the natural course and treatment response in patients with HCV infection are largely determined by complex host‑viral interactions. HCV genotype is the most important viral factor predicting the response to pegylated interferon‑α plus ribavirin therapy. The subtype of HCV genotype 1 is the key viral factor that predicts the efficacy of direct‑acting antiviral therapy...
March 22, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28334294/an-examination-of-the-role-of-l-glutamate-and-inosine-5-monophosphate-in-hedonic-taste-guided-behavior-by-mice-lacking-the-t1r1-t1r3-receptor
#16
Ginger D Blonde, Alan C Spector
The heterodimeric T1R1 + T1R3 receptor is considered critical for normal signaling of L-glutamate and 5'-ribonucleotides in the oral cavity. However, some taste-guided responsiveness remains in mice lacking one subunit of the receptor, suggesting that other receptors are sufficient to support some behaviors. Here, mice lacking both receptor subunits (KO) and wild-type (WT, both n = 13) mice were tested in a battery of behavioral tests. Mice were trained and tested in gustometers with a concentration series of Maltrin-580, a maltodextrin, in a brief-access test (10-s trials) as a positive control...
March 17, 2017: Chemical Senses
https://www.readbyqxmd.com/read/28330104/purification-and-characterization-of-the-enzymes-involved-in-nicotinamide-adenine-dinucleotide-degradation-by-penicillium-brevicompactum-nrc-829
#17
Thanaa Hamed Ali, Dina Helmy El-Ghonemy
The present study was conducted to investigate a new pathway for the degradation of nicotinamide adenine dinucleotide (NAD) by Penicillium brevicompactum NRC 829 extracts. Enzymes involved in the hydrolysis of NAD, i.e. alkaline phosphatase, aminohydrolase and glycohydrolase were determined. Alkaline phosphatase was found to catalyse the sequential hydrolysis of two phosphate moieties of NAD molecule to nicotinamide riboside plus adenosine. Adenosine was then deaminated by aminohydrolase to inosine and ammonia...
June 2016: 3 Biotech
https://www.readbyqxmd.com/read/28325731/effects-of-genetic-deletion-of-soluble-5-nucleotidases-nt5c1a-and-nt5c2-on-ampk-activation-and-nucleotide-levels-in-contracting-mouse-skeletal-muscles
#18
Samanta Kviklyte, Didier Vertommen, Xavier Yerna, Harriet Andersén, Xiufeng Xu, Philippe Gailly, Mohammad Bohlooly-Y, Jan Oscarsson, Mark H Rider
AMP-activated protein kinase (AMPK) plays a key role in energy homeostasis and is activated in response to contraction-induced ATP depletion in skeletal muscle via a rise in intracellular AMP/ADP concentrations. AMP can be deaminated by AMP-deaminase to IMP, which is hydrolysed to inosine by cytosolic 5'-nucleotidase-II (NT5C2). AMP can also be hydrolysed to adenosine by cytosolic 5'-nucleotidase-IA (NT5C1A). Previous gene silencing and overexpression studies indicated control of AMPK activation by NT5C enzymes...
March 21, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28303227/analysis-of-cordyceps-by-multi-column-liquid-chromatography
#19
Zhengming Qian, Shaoping Li
Cordyceps is a famous traditional Chinese medicine (TCM) that has been used in China for hundreds of years. In the present study a multi-column liquid chromatography (MC-LC) system was developed for the qualitative analysis of macromolecules and micromolecules in Cordyceps. The MC-LC system includes a size exclusion pre-column, a size exclusion column (SEC) and a reversed phase column (RP) which were controlled by column-switching valves. The sample was separated by the size exclusion pre-column into two fractions (macromolecules and micromolecules)...
March 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/28298229/a-novel-benzo-heterocyclic-amine-derivative-n30-inhibits-influenza-virus-replication-by-depression-of-inosine-5-monophospate-dehydrogenase-activity
#20
Jin Hu, Linlin Ma, Huiqiang Wang, Haiyan Yan, Dajun Zhang, Zhuorong Li, Jiandong Jiang, Yuhuan Li
BACKGROUD: Influenza virus is still a huge threat to the world-wide public health. Host inosine-5'- monophosphate dehydrogenase (IMPDH) involved in the synthesis of guanine nucleotides, is known to be a potential target to inhibit the replication of viruses. Herein, we evaluated antiviral activity of a benzo-heterocyclic amine derivative N30, which was designed to inhibit IMPDH. RESULTS: The results demonstrated that N30 inhibited the replication of H1N1, H3N2, influenza B viruses, including oseltamivir and amantadine resistant strains in vitro...
March 15, 2017: Virology Journal
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