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RNA methylation

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https://www.readbyqxmd.com/read/29792884/pharmacological-inhibition-of-dna-methylation-attenuates-pressure-overload-induced-cardiac-hypertrophy-in-rats
#1
Justus Stenzig, Yvonne Schneeberger, Alexandra Löser, Barbara S Peters, Andreas Schaefer, Rong-Rong Zhao, Shi Ling Ng, Grit Höppner, Birgit Geertz, Marc N Hirt, Wilson Tan, Eleanor Wong, Hermann Reichenspurner, Roger S-Y Foo, Thomas Eschenhagen
BACKGROUND: Heart failure is associated with altered gene expression and DNA methylation. De novo DNA methylation is associated with gene silencing, but its role in cardiac pathology remains incompletely understood. We hypothesized that inhibition of DNA methyltransferases (DNMT) might prevent the deregulation of gene expression and the deterioration of cardiac function under pressure overload (PO). To test this hypothesis, we evaluated a DNMT inhibitor in PO in rats and analysed DNA methylation in cardiomyocytes...
May 21, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29792227/integrated-time-course-omics-analysis-distinguishes-immediate-therapeutic-response-from-acquired-resistance
#2
Genevieve Stein-O'Brien, Luciane T Kagohara, Sijia Li, Manjusha Thakar, Ruchira Ranaweera, Hiroyuki Ozawa, Haixia Cheng, Michael Considine, Sandra Schmitz, Alexander V Favorov, Ludmila V Danilova, Joseph A Califano, Evgeny Izumchenko, Daria A Gaykalova, Christine H Chung, Elana J Fertig
BACKGROUND: Targeted therapies specifically act by blocking the activity of proteins that are encoded by genes critical for tumorigenesis. However, most cancers acquire resistance and long-term disease remission is rarely observed. Understanding the time course of molecular changes responsible for the development of acquired resistance could enable optimization of patients' treatment options. Clinically, acquired therapeutic resistance can only be studied at a single time point in resistant tumors...
May 23, 2018: Genome Medicine
https://www.readbyqxmd.com/read/29790249/the-mechanisms-of-epigenetic-inheritance-how-diverse-are-they
#3
Oleg N Tikhodeyev
Although epigenetic inheritance (EI) is a rapidly growing field of modern biology, it still has no clear place in fundamental genetic concepts which are traditionally based on the hereditary role of DNA. Moreover, not all mechanisms of EI attract the same attention, with most studies focused on DNA methylation, histone modification, RNA interference and amyloid prionization, but relatively few considering other mechanisms such as stable inhibition of plastid translation. Herein, we discuss all known and some hypothetical mechanisms that can underlie the stable inheritance of phenotypically distinct hereditary factors that lack differences in DNA sequence...
May 22, 2018: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/29789810/rna-from-trained-aplysia-can-induce-an-epigenetic-engram-for-long-term-sensitization-in-untrained-aplysia
#4
Alexis Bédécarrats, Shanping Chen, Kaycey Pearce, Diancai Cai, David L Glanzman
The precise nature of the engram, the physical substrate of memory, remains uncertain. Here, it is reported that RNA extracted from the central nervous system of Aplysia given long-term sensitization (LTS) training induced sensitization when injected into untrained animals; furthermore, the RNA-induced sensitization, like training-induced sensitization, required DNA methylation. In cellular experiments, treatment with RNA extracted from trained animals was found to increase excitability in sensory neurons, but not in motor neurons, dissociated from naïve animals...
May 2018: ENeuro
https://www.readbyqxmd.com/read/29789295/integration-of-protein-phosphorylation-acetylation-and-methylation-data-sets-to-outline-lung-cancer-signaling-networks
#5
Mark Grimes, Benjamin Hall, Lauren Foltz, Tyler Levy, Klarisa Rikova, Jeremiah Gaiser, William Cook, Ekaterina Smirnova, Travis Wheeler, Neil R Clark, Alexander Lachmann, Bin Zhang, Peter Hornbeck, Avi Ma'ayan, Michael Comb
Protein posttranslational modifications (PTMs) have typically been studied independently, yet many proteins are modified by more than one PTM type, and cell signaling pathways somehow integrate this information. We coupled immunoprecipitation using PTM-specific antibodies with tandem mass tag (TMT) mass spectrometry to simultaneously examine phosphorylation, methylation, and acetylation in 45 lung cancer cell lines compared to normal lung tissue and to cell lines treated with anticancer drugs. This simultaneous, large-scale, integrative analysis of these PTMs using a cluster-filtered network (CFN) approach revealed that cell signaling pathways were outlined by clustering patterns in PTMs...
May 22, 2018: Science Signaling
https://www.readbyqxmd.com/read/29789208/synthesis-of-4-c-aminoalkyl-2-o-methyl-modified-rna-and-their-biological-properties
#6
Kana Koizumi, Yusuke Maeda, Toshifumi Kano, Hisae Yoshida, Taiichi Sakamoto, Kenji Yamagishi, Yoshihito Ueno
In this paper, we describe the synthesis of 4'-C-aminoalkyl-2'-O-methylnucleosides and the properties of RNAs containing these analogs. Phosphoramidites of 4'-C-aminoethyl and 4'-C-aminopropyl-2'-O-methyluridines were prepared using glucose as starting material, and RNAs containing the analogs were synthesized using the phosphoramidites. Thermal denaturation studies revealed that these nucleoside analogs decreased the thermal stabilities of double-stranded RNAs (dsRNAs). Results of NMR, molecular modeling, and CD spectra measurements suggested that 4'-C-aminoalkyl-2'-O-methyluridine adopts an C2'-endo sugar puckering in dsRNA...
May 17, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29787246/investigation-of-solvent-hydron-exchange-in-the-reaction-catalyzed-by-the-antibiotic-resistance-protein-cfr
#7
Matthew R Bauerle, Tyler L Grove, Squire J Booker
Cfr is a radical S-adenosylmethionine (RS) methylase that appends methyl groups to C8 and C2 of adenosine 2503 in 23S ribosomal RNA. Methylation of C8 confers resistance to several classes of antibiotics that bind in or near the peptidyl transferase center of the bacterial ribosome, including the synthetic antibiotic linezolid. The Cfr reaction requires the action of five conserved cysteines, three of which ligate a required [4Fe-4S] cluster cofactor. The two remaining cysteines play a more intricate role in the reaction, one of which (Cys338) becoming transiently methylated during catalysis...
May 22, 2018: Biochemistry
https://www.readbyqxmd.com/read/29786071/dopamine-d2-receptor-restricts-astrocytic-nlrp3-inflammasome-activation-via-enhancing-the-interaction-of-%C3%AE-arrestin2-and-nlrp3
#8
Jialei Zhu, Zhaoli Hu, Xiaojuan Han, Dongshuo Wang, Qingling Jiang, Jianhua Ding, Ming Xiao, Cong Wang, Ming Lu, Gang Hu
Astrocytes are involved in the neuroinflammation of neurodegenerative diseases, such as Parkinson's disease (PD). Among the numerous inflammatory cytokines, interleukin-1β (IL-1β) produced by astrocytic Nod-like receptor protein (NLRP) inflammasome is crucial in the pathogenesis of PD. β-arrestin2-mediated dopamine D2 receptor (Drd2) signal transduction has been regarded as a potential anti-inflammatory target. Our previous study revealed that astrocytic Drd2 suppresses neuroinflammation in the central nervous system...
May 21, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29784880/arginine-methylation-of-translocated-in-liposarcoma-tls-inhibits-its-binding-to-long-noncoding-rna-abrogating-tls-mediated-repression-of-cbp-p300-activity
#9
Wei Cui, Ryoma Yoneda, Naomi Ueda, Riki Kurokawa
Translocated in liposarcoma (TLS) is an RNA-binding protein and a transcription-regulatory sensor of DNA damage. TLS binds promoter-associated noncoding RNA (pncRNA) and inhibits histone acetyltransferase (HAT) activity of CREB-binding protein (CBP)/E1A-binding protein P300 (p300) on the cyclin D1 (CCND1) gene. Although post-translational modifications of TLS, such as arginine methylation, are known to regulate TLS's nucleocytoplasmic shuttling and assembly in stress granules, its interactions with RNAs remain poorly characterized...
May 21, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29783144/analogous-modified-dna-probe-and-immune-competition-method-based-electrochemical-biosensor-for-rna-modification
#10
Tao Dai, Qinli Pu, Yongcan Guo, Chen Zuo, Shulian Bai, Yujun Yang, Dan Yin, Yi Li, Shangchun Sheng, Yiyi Tao, Jie Fang, Wen Yu, Guoming Xie
N6-methyladenosine (m6A), one of the most abundant RNA methylation which is ubiquitous in eukaryotic RNA, plays vital roles in many biological progresses. Therefore, the rapid and accurate quantitative detection of m6A is particularly important for its functional research. Herein, a label-free and highly selective electrochemical immunosensor was developed for the detection of m6A. The method is established on that the anti-m6A-Ab can recognize both m6A-RNA and m6A-DNA. An analogous modified DNA probe (L1) serves as a signal molecule, by competing with m6A-RNA for binding to Abs to broaden the linear range...
May 18, 2018: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29782652/adenosine-methylation-as-a-molecular-imprint-defining-the-fate-of-rna
#11
REVIEW
Philip Knuckles, Marc Bühler
Multiple lines of evidence suggest the RNA modification N6 -methyladonsine (m6 A), which is installed in the nucleus co-transcriptionally and, thereafter, serves as a reversible chemical imprint that influences several steps of mRNA metabolism. This includes but is not limited to RNA folding, splicing, stability, transport, and translation. In this Review we focus on the current view of the nuclear installation of m6 A as well the molecular players involved, the so called m6 A writers. We also explore the effector proteins, or m6 A readers, that decode the imprint in different cellular contexts and compartments, and ultimately, the way the modification influences the lifecycle of an RNA molecule...
May 21, 2018: FEBS Letters
https://www.readbyqxmd.com/read/29782154/miclip-mapseq-a-substrate-identification-approach-for-radical-sam-rna-methylating-enzymes
#12
Vanja Stojković, Tongyue Chu, Gabriel Therizols, David E Weinberg, Danica Galonić Fujimori
Although present across bacteria, the large family of radical SAM RNA methylating enzymes is largely uncharacterized. Escherichia coli RlmN, the founding member of the family, methylates an adenosine in 23S rRNA and several tRNAs to yield 2-methyladenosine (m2A). However, varied RNA substrate specificity among RlmN enzymes, combined with the ability of certain family members to generate 8-methyladenosine (m8A), makes functional predictions across this family challenging. Here, we present a method for unbiased substrate identification that exploits highly efficient, mechanism-based crosslinking between the enzyme and its RNA substrates...
May 21, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29780264/methylation-and-gene-expression-of-bcat1-and-ikzf1-in-colorectal-cancer-tissues
#13
Maher Jedi, Graeme P Young, Susanne K Pedersen, Erin L Symonds
The genes BCAT1 and IKZF1 are hypermethylated in colorectal cancer (CRC), but little is known about how this relates to gene expression. This study assessed the relationship between methylation and gene expression of BCAT1 and IKZF1 in CRC and adjacent non-neoplastic tissues. The tissues were obtained at surgery from 36 patients diagnosed with different stages of CRC (stage I n = 8, stage II n = 13, stage III n = 10, stage IV n = 5). Methylated BCAT1 and IKZF1 were detected in 92% and 72% CRC tissues, respectively, with levels independent of stage ( P  > ...
2018: Clinical Medicine Insights. Oncology
https://www.readbyqxmd.com/read/29778942/transcriptomic-and-methylomic-analysis-reveal-the-toxicological-effect-of-2-3-7-8-tetrachlorodibenzodioxin-on-human-embryonic-stem-cell
#14
Keng Po Lai, Jing Woei Li, Ting Fung Chan, Andy Chen, Cherie Yin Lau Lee, William Shu Biu Yeung, Chris Kong Chu Wong
Cumulating epidemiological studies demonstrated that environmental exposure to endocrine disrupting chemicals (EDCs) during the early stages of fetal development is associated with the increase in disease susceptibility in later life. The fetal developmental plasticity is considered as a protective mechanism against an undesirable prenatal environment. Dioxin is one of the environmental contaminants and is considered a diabetogenic factor. Experimental animal and human epidemiological studies have revealed that dioxin exposure was associated with insulin resistance and altered beta cell function...
May 10, 2018: Chemosphere
https://www.readbyqxmd.com/read/29777364/cell-division-and-turgor-mediate-enhanced-plant-growth-in-arabidopsis-plants-treated-with-the-bacterial-signalling-molecule-lumichrome
#15
Motlalepula Pholo, Beatrix Coetzee, Hans J Maree, Philip R Young, James R Lloyd, Jens Kossmann, Paul N Hills
Transcriptomic analysis indicates that the bacterial signalling molecule lumichrome enhances plant growth through a combination of enhanced cell division and cell enlargement, and possibly enhances photosynthesis. Lumichrome (7,8 dimethylalloxazine), a novel multitrophic signal molecule produced by Sinorhizobium meliloti bacteria, has previously been shown to elicit growth promotion in different plant species (Phillips et al. in Proc Natl Acad Sci USA 96:12275-12280, https://doi.org/10.1073/pnas.96.22.12275 , 1999)...
May 17, 2018: Planta
https://www.readbyqxmd.com/read/29777057/glycogen-synthase-kinase-3-gsk-3-activity-regulates-mrna-methylation-in-mouse-embryonic-stem-cells
#16
Kelsie J Faulds, Jennifer N Egelston, Laura J Sedivy, Matthew K Mitchell, Sanjana Garimella, Hanna Kozlowski, Angelo D'Alessandro, Kirk C Hansen, Jeremy L Balsbaugh, Christopher J Phiel
Glycogen synthase kinase-3 (Gsk-3) activity regulates multiple signal transduction pathways, and is also a key component of the network responsible for maintaining stem cell pluripotency. Genetic deletion of Gsk-3α and Gsk-3β or inhibition of Gsk-3 activity via small molecules promotes stem cell pluripotency, yet the mechanism underlying the role for Gsk-3 in this process remains ambiguous. Another cellular process that has been shown to affect stem cell pluripotency is mRNA methylation (m6 A). Here, we describe an intersection between these components - the regulation of m6 A by Gsk-3...
May 18, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29775108/high-trna-transferase-nsun2-gene-expression-is-associated-with-poor-prognosis-in-head-and-neck-squamous-carcinoma
#17
Lingeng Lu, Gongjian Zhu, Hongmei Zeng, Qian Xu, Klaus Holzmann
NSUN2 is a tRNA methyltransferase and plays an important role in cell development via modifying RNA methylation. We aimed to evaluate the expression of NSUN2 and its prognostic value in HNSCC. Random-effects model of meta-analysis shows 1.99-folds (95% CI: 1.89-2.09) upregulation of NSUN2 expression in HNSCC versus normal tissues. Patients with high NSUN2 levels had approximately 22 months shorter overall survival, and had a higher mortality risk than those with low one (p-trend = 0.020). In conclusion, NSUN2 is a potential independent prognostic marker and may be a potential therapeutic target in HNSCC...
April 21, 2018: Cancer Investigation
https://www.readbyqxmd.com/read/29774127/paf1-complex-interactions-with-setdb1-mediate-promoter-h3k9-methylation-and-transcriptional-repression-of-hoxa9-and-meis1-in-acute-myeloid-leukemia
#18
James Ropa, Nirmalya Saha, Zhiling Chen, Justin Serio, Wei Chen, Dattatreya Mellacheruvu, Lili Zhao, Venkatesha Basrur, Alexey I Nesvizhskii, Andrew G Muntean
The Polymerase Associated Factor 1 complex (PAF1c) is an epigenetic co-modifying complex that directly contacts RNA polymerase II (RNAPII) and several epigenetic regulating proteins. Mutations, overexpression and loss of expression of subunits of the PAF1c are observed in various forms of cancer suggesting proper regulation is needed for cellular development. However, the biochemical interactions with the PAF1c that allow dynamic gene regulation are unclear. We and others have shown that the PAF1c makes a direct interaction with MLL fusion proteins, which are potent oncogenic drivers of acute myeloid leukemia (AML)...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29773918/rna-modifying-proteins-as-anticancer-drug-targets
#19
REVIEW
P Ann Boriack-Sjodin, Scott Ribich, Robert A Copeland
All major biological macromolecules (DNA, RNA, proteins and lipids) undergo enzyme-catalysed covalent modifications that impact their structure, function and stability. A variety of covalent modifications of RNA have been identified and demonstrated to affect RNA stability and translation to proteins; these mechanisms of translational control have been termed epitranscriptomics. Emerging data suggest that some epitranscriptomic mechanisms are altered in human cancers as well as other human diseases. In this Review, we examine the current understanding of RNA modifications with a focus on mRNA methylation, highlight their possible roles in specific cancer indications and discuss the emerging potential of RNA-modifying proteins as therapeutic targets...
May 18, 2018: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/29773832/distinct-epigenetic-landscapes-underlie-the-pathobiology-of-pancreatic-cancer-subtypes
#20
Gwen Lomberk, Yuna Blum, Rémy Nicolle, Asha Nair, Krutika Satish Gaonkar, Laetitia Marisa, Angela Mathison, Zhifu Sun, Huihuang Yan, Nabila Elarouci, Lucile Armenoult, Mira Ayadi, Tamas Ordog, Jeong-Heon Lee, Gavin Oliver, Eric Klee, Vincent Moutardier, Odile Gayet, Benjamin Bian, Pauline Duconseil, Marine Gilabert, Martin Bigonnet, Stephane Garcia, Olivier Turrini, Jean-Robert Delpero, Marc Giovannini, Philippe Grandval, Mohamed Gasmi, Veronique Secq, Aurélien De Reyniès, Nelson Dusetti, Juan Iovanna, Raul Urrutia
Recent studies have offered ample insight into genome-wide expression patterns to define pancreatic ductal adenocarcinoma (PDAC) subtypes, although there remains a lack of knowledge regarding the underlying epigenomics of PDAC. Here we perform multi-parametric integrative analyses of chromatin immunoprecipitation-sequencing (ChIP-seq) on multiple histone modifications, RNA-sequencing (RNA-seq), and DNA methylation to define epigenomic landscapes for PDAC subtypes, which can predict their relative aggressiveness and survival...
May 17, 2018: Nature Communications
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