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Posttranscriptional modification

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https://www.readbyqxmd.com/read/28521327/epigenomics-pharmacoepigenomics-and-personalized-medicine-in-cervical-cancer
#1
Shama Prasada Kabekkodu, Sanjiban Chakrabarty, Supriti Ghosh, Angela Brand, Kapaettu Satyamoorthy
Epigenomics encompasses the study of genome-wide changes in DNA methylation, histone modifications and noncoding RNAs leading to altered transcription, chromatin structure, and posttranscription RNA processing, respectively, resulting in an altered rate of gene expression. The role of epigenetic modifications facilitating human diseases is well established. Previous studies have identified histone and cytosine code during normal and pathological conditions with special emphasis on how these modifications regulate transcriptional events...
May 19, 2017: Public Health Genomics
https://www.readbyqxmd.com/read/28484874/effects-of-arsenic-toxicity-beyond-epigenetic-modifications
#2
REVIEW
Geir Bjørklund, Jan Aaseth, Salvatore Chirumbolo, Mauricio A Urbina, Riaz Uddin
Worldwide chronic arsenic (As) poisoning by arsenic-contaminated groundwater is one of the most threatening public health problems. Chronic inorganic As (inAs) exposure has been associated with various forms of cancers and numerous other pathological effects in humans, collectively known as arsenicosis. Over the past decade, evidence indicated that As-induced epigenetic modifications have a role in the adverse effects on human health. The main objective of this article is to review the evidence on epigenetic modifications induced by arsenicals...
May 8, 2017: Environmental Geochemistry and Health
https://www.readbyqxmd.com/read/28484591/brothers-in-arms-emerging-roles-of-rna-epigenetics-in-dna-damage-repair
#3
Jinwei Zhang
N6-methyladenosine (m(6)A) is a widespread posttranscriptional RNA modification that occurs in tRNA, rRNA, snRNA, viral RNAs, and more recently is shown to occur in mRNA in a dynamic, reversible manner. At the epicenter of RNA epigenetics, m(6)A influences essentially all stages of RNA metabolism. As a result, m(6)A modulates cell differentiation and pluripotency, cell cycle and tumorigenesis, and several types of stress responses, etc. A recent report by Shi and colleagues uncovers a novel pathway in which m(6)A RNA, its associated enzymes, and DNA polymerase κ constitute an early-response system that confers cellular resistance to ultraviolet irradiation, separate from the canonical nucleotide excision repair (NER) pathway that normally repairs UV-induced DNA damage...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/28441146/epigenetic-regulation-of-glucose-metabolism
#4
Sapna Sharma, Jennifer Kriebel, Harald Grallert
PURPOSE OF REVIEW: Glucose metabolism is a central process in mammalian energy homeostasis. Its deregulation is a key factor in development of metabolic disease like diabetes and cancer. In recent decades, our understanding of gene regulation at the signaling, chromatin and posttranscriptional levels has seen dramatic developments. RECENT FINDINGS: A number of epigenetic mechanisms that do not affect the genetic code can be assessed with new technologies. However, increasing complexity becomes a major challenge for translation into clinical application...
April 24, 2017: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/28439027/biochemical-and-structural-characterization-of-oxygen-sensitive-2-thiouridine-synthesis-catalyzed-by-an-iron-sulfur-protein-ttua
#5
Minghao Chen, Shin-Ichi Asai, Shun Narai, Shusuke Nambu, Naoki Omura, Yuriko Sakaguchi, Tsutomu Suzuki, Masao Ikeda-Saito, Kimitsuna Watanabe, Min Yao, Naoki Shigi, Yoshikazu Tanaka
Two-thiouridine (s(2)U) at position 54 of transfer RNA (tRNA) is a posttranscriptional modification that enables thermophilic bacteria to survive in high-temperature environments. s(2)U is produced by the combined action of two proteins, 2-thiouridine synthetase TtuA and 2-thiouridine synthesis sulfur carrier protein TtuB, which act as a sulfur (S) transfer enzyme and a ubiquitin-like S donor, respectively. Despite the accumulation of biochemical data in vivo, the enzymatic activity by TtuA/TtuB has rarely been observed in vitro, which has hindered examination of the molecular mechanism of S transfer...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28435892/dramatic-improvement-of-crispr-cas9-editing-in-candida-albicans-by-increased-single-guide-rna-expression
#6
Henry Ng, Neta Dean
The clustered regularly interspaced short palindromic repeat system with CRISPR-associated protein 9 nuclease (CRISPR/Cas9) has emerged as a versatile tool for genome editing in Candida albicans. Mounting evidence from other model systems suggests that the intracellular levels of single guide RNA (sgRNA) limit the efficiency of Cas9-dependent DNA cleavage. Here, we tested this idea and describe a new means of sgRNA delivery that improves previously described methods by ~10-fold. The efficiency of Cas9/sgRNA-dependent cleavage and repair of a single-copy yeast enhanced monomeric red fluorescent protein (RFP) gene was measured as a function of various parameters that are hypothesized to affect sgRNA accumulation, including transcriptional and posttranscriptional processing...
March 2017: MSphere
https://www.readbyqxmd.com/read/28432181/dual-nature-of-pseudouridylation-in-u2-snrna-pus1p-dependent-and-pus1p-independent-activities-in-yeasts-and-higher-eukaryotes
#7
Svetlana Deryusheva, Joseph G Gall
The pseudouridine at position 43 in vertebrate U2 snRNA is one of the most conserved posttranscriptional modifications of spliceosomal snRNAs; the equivalent position is pseudouridylated in U2 snRNAs in different phyla including fungi, insects, and worms. Pseudouridine synthase Pus1p acts alone on U2 snRNA to form this pseudouridine in yeast Saccharomyces cerevisiae and mouse. Furthermore, in S. cerevisiae Pus1p is the only pseudouridine synthase for this position. Using an in vivo yeast cell system we tested enzymatic activity of Pus1p from the fission yeast Schizosaccharomyces pombe, the worm Caenorhabditis elegans, the fruit fly Drosophila melanogaster and the frog Xenopus tropicalis...
April 21, 2017: RNA
https://www.readbyqxmd.com/read/28401060/therapeutic-targeting-of-histone-modifications-in-adult-and-pediatric-high-grade-glioma
#8
REVIEW
Maria J Williams, Will G B Singleton, Stephen P Lowis, Karim Malik, Kathreena M Kurian
Recent exciting work partly through The Cancer Genome Atlas has implicated epigenetic mechanisms including histone modifications in the development of both pediatric and adult high-grade glioma (HGG). Histone lysine methylation has emerged as an important player in regulating gene expression and chromatin function. Lysine (K) 27 (K27) is a critical residue in all seven histone 3 variants and the subject of posttranslational histone modifications, as it can be both methylated and acetylated. In pediatric HGG, two critical single-point mutations occur in the H3F3A gene encoding the regulatory histone variant H3...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28392787/bioconjugation-of-small-molecules-to-rna-impedes-its-recognition-by-toll-like-receptor-7
#9
Isabell Hellmuth, Isabel Freund, Janine Schlöder, Salifu Seidu-Larry, Kathrin Thüring, Kaouthar Slama, Jens Langhanki, Stefka Kaloyanova, Tatjana Eigenbrod, Matthias Krumb, Sandra Röhm, Kalina Peneva, Till Opatz, Helmut Jonuleit, Alexander H Dalpke, Mark Helm
A fundamental mechanism of the innate immune system is the recognition, via extra- and intracellular pattern-recognition receptors, of pathogen-associated molecular patterns. A prominent example is represented by foreign nucleic acids, triggering the activation of several signaling pathways. Among these, the endosomal toll-like receptor 7 (TLR7) is known to be activated by single-stranded RNA (ssRNA), which can be specifically influenced through elements of sequence structure and posttranscriptional modifications...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28353398/a-fly-view-on-the-roles-and-mechanisms-of-the-m-6-a-mrna-modification-and-its-players
#10
Tina Lence, Matthias Soller, Jean-Yves Roignant
RNA modifications are an emerging layer of posttranscriptional gene regulation in eukaryotes. N(6)-methyladenosine (m(6)A) is among the most abundant modifications in mRNAs (mRNAs) that was shown to influence many physiological processes from yeast to mammals. Like DNA methylation, m(6)A in mRNA is dynamically regulated. A conserved methyltransferase complex catalyzes the deposition of the methyl group on adenosine, which can be removed by specific classes of demethylases. Furthermore, YTH-domain containing proteins can recognize this modification to mediate m(6)A-dependent activities...
March 29, 2017: RNA Biology
https://www.readbyqxmd.com/read/28349465/transcriptome-wide-mapping-of-n-1-methyladenosine-methylome
#11
Xiaoyu Li, Jinying Peng, Chengqi Yi
N (1)-Methyladenosine (m(1)A) is a prevalent posttranscriptional RNA modification and commonly found in tRNA and rRNA. Very recent works have also demonstrated the prevalence of m(1)A in mammalian mRNA. Hence, high-throughput methods that allow transcriptome-wide mapping of m(1)A will be important for further functional investigations. Here, we describe a technique called "m(1)A-ID-Seq", which is based on m(1)A immunoprecipitation and the inherent ability of m(1)A to stall reverse transcription, to map m(1)A in the transcriptome...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28349432/induction-of-transcriptional-gene-silencing-by-expression-of-shrna-directed-to-c-myc-p2-promoter-in-hepatocellular-carcinoma-by-tissue-specific-virosomal-delivery
#12
Mohammad Khalid Zakaria, Debi P Sarkar, Parthaprasad Chattopadhyay
Double-stranded RNA-mediated transcriptional gene silencing (TGS) has shown promising results over posttranscriptional gene silencing (PTGS) due to its long term and heritable nature. Various research groups have shed light on different mechanisms by which TGS operate. Some of these include histone modification, DNA methylation, or restriction of RNA polymerase binding onto the target gene's promoter. This serves as an added advantage since permanent c-Myc inactivation is critical for suppressing hepatocellular carcinoma (HCC)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28345525/tolerance-of-monocytes-and-macrophages-in-response-to-bacterial-endotoxin
#13
Ewelina Wiśnik, Ewa Pikus, Piotr Duchnowicz, Maria Koter-Michalak
Monocytes belong to myeloid effector cells, which constitute the first line of defense against pathogens, also called the nonspecific immune system and play an important role in the maintenance of tissue homeostasis. In response to stimulation, monocytes differentiate into macrophages capable of microorganism phagocytosis and secrete factors that play a key role in the regulation of immune responses. However excessive exposure of monocytes/macrophages to the lipopolysaccharide (LPS) of Gram negative bacteria leads to the acquisition of immune tolerance by these cells...
March 7, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28280365/downregulation-of-long-noncoding-rna-hotairm1-promotes-monocyte-dendritic-cell-differentiation-through-competitively-binding-to-endogenous-mir-3960
#14
Jiaxuan Xin, Jing Li, Yue Feng, Liyang Wang, Yuan Zhang, Rongcun Yang
Myeloid differentiation is controlled by a multilayered regulatory circuitry consisting of various elements, including histone modifications, transcription factors, and posttranscriptional regulators such as miRNAs, long noncoding RNAs, and circular RNAs. However, the molecular mechanism underlying this biological process remains unclear. In this study, through epigenetic profiling analysis using chromatin immunoprecipitation (ChIP) followed by sequencing (ChIP-seq), we identified an lncRNA, HOTAIRM1, with a critical role in myeloid development...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28278381/alternative-splicing-of-stat3-is-affected-by-rna-editing
#15
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/28277930/wobble-uridine-modifications-a-reason-to-live-a-reason-to-die
#16
Raffael Schaffrath, Sebastian A Leidel
Wobble uridines (U34) are generally modified in all species. U34 modifications can be essential in metazoans but are not required for viability in fungi. In this review, we provide an overview on the types of modifications and how they affect the physico-chemical properties of wobble uridines. We describe the molecular machinery required to introduce these modifications into tRNA posttranscriptionally and discuss how posttranslational regulation may affect the activity of the modifying enzymes. We highlight the activity of anticodon specific RNases that target U34 containing tRNA...
February 23, 2017: RNA Biology
https://www.readbyqxmd.com/read/28263563/alkyne-functionalized-coumarin-compound-for-analytic-and-preparative-4-thiouridine-labeling
#17
Katharina Schmid, Maria Adobes-Vidal, Mark Helm
Bioconjugation of RNA is a dynamic field recently reinvigorated by a surge in research on post-transcriptional modification. This work focuses on the bioconjugation of 4-thiouridine, a nucleoside that occurs as a post-transcriptional modification in bacterial RNA and is used as a metabolic label and for cross-linking purposes in eukaryotic RNA. A newly designed coumarin compound named 4-bromomethyl-7-propargyloxycoumarin (PBC) is introduced, which exhibits remarkable selectivity for 4-thiouridine. Bearing a terminal alkyne group, it is conductive to secondary bioconjugation via "click chemistry", thereby offering a wide range of preparative and analytical options...
March 15, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28247053/cell-fate-maintenance-and-reprogramming-during-the-oocyte-to-embryo-transition
#18
Christina Fassnacht, Rafal Ciosk
This chapter reviews our current understanding of the mechanisms that regulate reprogramming during the oocyte-to-embryo transition (OET). There are two major events reshaping the transcriptome during OET. One is the clearance of maternal transcripts in the early embryo, extensively reviewed by others. The other event, which is the focus of this chapter, is the embryonic (or zygotic) genome activation (EGA). The mechanisms controlling EGA can be broadly divided into transcriptional and posttranscriptional. The former includes the regulation of the basal transcription machinery, the regulation by specific transcription factors and chromatin modifications...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/28202819/-melas-mitochondrial-encephalomyopathy-lactic-acidosis-and-stroke-like-episodes
#19
Hidetomo Murakami, Kenjiro Ono
Mitochondrial disease is caused by a deficiency in the energy supply to cells due to mitochondrial dysfunction. Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) is a mitochondrial disease that presents with stroke-like episodes such as acute onset of neurological deficits and characteristic imaging findings. Stroke-like episodes in MELAS have the following features: 1) neurological deficits due to localization of lesions in the brain, 2) episodes often accompany epilepsy, 3) lesions do not follow the vascular supply area, 4) lesions are more often seen in the posterior brain than in the anterior brain, 5) lesions spread to an adjacent area in the brain, and 6) neurological symptoms often disappear together with imaging findings, but later relapse...
February 2017: Brain and Nerve, Shinkei Kenkyū No Shinpo
https://www.readbyqxmd.com/read/28149289/pore-forming-proteins-as-mediators-of-novel-epigenetic-mechanism-of-epilepsy
#20
Andrei Surguchov, Irina Surgucheva, Mukut Sharma, Ram Sharma, Vikas Singh
Epilepsy is a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures. In the last two decades, numerous gene defects underlying different forms of epilepsy have been identified with most of these genes encoding ion channel proteins. Despite these developments, the etiology of majority of non-familial epilepsies has no known associated genetic mutations and cannot be explained by defects in identified ion channels alone. We hypothesize that de novo formation of ion channels by naturally unfolded proteins (NUPs) increases neuronal excitability...
2017: Frontiers in Neurology
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