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RNA methylation

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https://www.readbyqxmd.com/read/27922002/targeting-the-notch-regulated-non-coding-rna-tug1-for-glioma-treatment
#1
Keisuke Katsushima, Atsushi Natsume, Fumiharu Ohka, Keiko Shinjo, Akira Hatanaka, Norihisa Ichimura, Shinya Sato, Satoru Takahashi, Hiroshi Kimura, Yasushi Totoki, Tatsuhiro Shibata, Mitsuru Naito, Hyun Jin Kim, Kanjiro Miyata, Kazunori Kataoka, Yutaka Kondo
Targeting self-renewal is an important goal in cancer therapy and recent studies have focused on Notch signalling in the maintenance of stemness of glioma stem cells (GSCs). Understanding cancer-specific Notch regulation would improve specificity of targeting this pathway. In this study, we find that Notch1 activation in GSCs specifically induces expression of the lncRNA, TUG1. TUG1 coordinately promotes self-renewal by sponging miR-145 in the cytoplasm and recruiting polycomb to repress differentiation genes by locus-specific methylation of histone H3K27 via YY1-binding activity in the nucleus...
December 6, 2016: Nature Communications
https://www.readbyqxmd.com/read/27916575/circannual-and-circadian-rhythms-of-hypothalamic-dna-methyltransferase-and-histone-deacetylase-expression-in-male-siberian-hamsters-phodopus-sungorus
#2
Tyler J Stevenson
Precise timing of gene transcription is a fundamental component of many biological rhythms. DNA methylation and histone acetylation are two epigenetic modifications that can affect the probability of gene transcription and RNA expression. Enzymes involved in DNA methylation (dnmts) have been shown to exhibit photoperiodic rhythms in expression in the hypothalamus, which coincide with hypothalamic expression of deiodinase type III (dio3), a gene involved in the photoperiodic regulation of reproduction. It is currently unknown whether enzymes involved in histone deacetylation (hdacs) also vary in response to photoperiod, nor have seasonal changes in the circadian waveforms of methylation and/or acetylation enzymes been examined...
December 1, 2016: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/27913729/qsea-modelling-of-genome-wide-dna-methylation-from-sequencing-enrichment-experiments
#3
Matthias Lienhard, Sabrina Grasse, Jana Rolff, Steffen Frese, Uwe Schirmer, Michael Becker, Stefan Börno, Bernd Timmermann, Lukas Chavez, Holger Sültmann, Gunda Leschber, Iduna Fichtner, Michal R Schweiger, Ralf Herwig
Genome-wide enrichment of methylated DNA followed by sequencing (MeDIP-seq) offers a reasonable compromise between experimental costs and genomic coverage. However, the computational analysis of these experiments is complex, and quantification of the enrichment signals in terms of absolute levels of methylation requires specific transformation. In this work, we present QSEA, Quantitative Sequence Enrichment Analysis, a comprehensive workflow for the modelling and subsequent quantification of MeDIP-seq data...
December 1, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27911846/dna-methylome-of-the-20-gigabase-norway-spruce-genome
#4
Israel Ausin, Suhua Feng, Chaowei Yu, Wanlu Liu, Hsuan Yu Kuo, Elise L Jacobsen, Jixian Zhai, Javier Gallego-Bartolome, Lin Wang, Ulrika Egertsdotter, Nathaniel R Street, Steven E Jacobsen, Haifeng Wang
DNA methylation plays important roles in many biological processes, such as silencing of transposable elements, imprinting, and regulating gene expression. Many studies of DNA methylation have shown its essential roles in angiosperms (flowering plants). However, few studies have examined the roles and patterns of DNA methylation in gymnosperms. Here, we present genome-wide high coverage single-base resolution methylation maps of Norway spruce (Picea abies) from both needles and somatic embryogenesis culture cells via whole genome bisulfite sequencing...
November 28, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911188/tuning-the-ribosome-the-influence-of-rrna-modification-on-eukaryotic-ribosome-biogenesis-and-function
#5
Katherine E Sloan, Ahmed S Warda, Sunny Sharma, Karl-Dieter Entian, Denis L J Lafontaine, Markus T Bohnsack
Ribosomal RNAs are extensively modified during their transcription and subsequent maturation in the nucleolus, nucleus and cytoplasm. RNA modifications, which are installed either by snoRNA-guided or by stand-alone enzymes, generally stabilise the structure of the ribosome. However, they also cluster at functionally important sites of the ribosome, such as the peptidyltransferase centre and the decoding site, where they facilitate efficient and accurate protein synthesis. The recent identification of sites of substoichiometric 2'-O-methylation and pseudouridylation has overturned the notion that all rRNA modifications are constitutively present on ribosomes, highlighting nucleotide modifications as an important source of ribosomal heterogeneity...
December 2, 2016: RNA Biology
https://www.readbyqxmd.com/read/27910903/prostate-cancer-patients-negative-biopsy-controls-discrimination-by-untargeted-metabolomics-analysis-of-urine-by-lc-qtof-upstream-information-on-other-omics
#6
M A Fernández-Peralbo, E Gómez-Gómez, M Calderón-Santiago, J Carrasco-Valiente, J Ruiz-García, M J Requena-Tapia, M D Luque de Castro, F Priego-Capote
The existing clinical biomarkers for prostate cancer (PCa) diagnosis are far from ideal (e.g., the prostate specific antigen (PSA) serum level suffers from lack of specificity, providing frequent false positives leading to over-diagnosis). A key step in the search for minimum invasive tests to complement or replace PSA should be supported on the changes experienced by the biochemical pathways in PCa patients as compared to negative biopsy control individuals. In this research a comprehensive global analysis by LC-QTOF was applied to urine from 62 patients with a clinically significant PCa and 42 healthy individuals, both groups confirmed by biopsy...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27909050/notch-pathway-is-activated-via-genetic-and-epigenetic-alterations-and-is-a-therapeutic-target-in-clear-cell-renal-cancer
#7
Tushar D Bhagat, Yiyu Zou, Shizeng Huang, Jihwan Park, Matthew B Palmer, Caroline Hu, Wejuan Li, Niraj Shenoy, Orsolya Giricz, Gaurav Choudhary, Yiting Yu, Yi-An Ko, Maria C Izquierdo, Ae Seo Deok Park, Nishanth Vallumsetla, Remi Laurence, Robert Lopez, Masako Suzuki, James Pullman, Justin Kaner, Benjamin Gartrell, A Ari Hakimi, John M Greally, Bharvin Patel, Karim Benhadji, Kith Pradhan, Amit Verma, Katalin Susztak
Clear cell renal cell carcinoma (CCRCC) is an incurable malignancy in advanced stages and needs newer therapeutic targets. Transcriptomic analysis of CCRCCs and matched microdissected renal tubular controls revealed overexpression of NOTCH ligands and receptors in tumor tissues. Examination of the TCGA RNA-seq dataset also revealed widespread activation of NOTCH pathway in a large cohort of CCRCC samples. Samples with NOTCH pathway activation were also clinically distinct and were associated with better overall survival...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27906710/who-s-your-daddy-paternal-inheritance-of-metabolic-disease-risk
#8
Elvira Isganaitis, Harumi Suehiro, Connie Cardona
PURPOSE OF REVIEW: Although the importance of optimizing mothers' health prior to conception and during pregnancy is now well accepted, recent data also implicate health and nutritional status of fathers as contributors to chronic disease risk in their progeny. This brief review will highlight recent epidemiological and experimental studies linking paternal overnutrition, undernutrition, and other forms of stress, to metabolic disease in the offspring. RECENT FINDINGS: The past 2 years have brought tremendous insights into the mechanisms by which paternal exposures can contribute to disease susceptibility in the next generation...
November 30, 2016: Current Opinion in Endocrinology, Diabetes, and Obesity
https://www.readbyqxmd.com/read/27906622/sensitive-liquid-chromatography-mass-spectrometry-lc-ms-assay-reveals-novel-insights-on-dna-methylation-and-incorporation-of-gemcitabine-its-metabolite-difluorodeoxyuridine-deoxyuridine-and-rx-3117-into-dna
#9
Richard J Honeywell, Dzjemma Sarkisjan, Ietje Kathmann, Michael H Kristensen, Godefridus J Peters
Antimetabolites are incorporated into DNA and RNA, affecting their function. Liquid-chromatography-mass-spectrometry (LC-MS-MS) permits the sensitive, selective analysis of normal nucleosides. The method was adapted to measure the incorporation of deoxyuridine, gemcitabine (difluorodeoxycytidine), its metabolite difluorodeoxyuridine (dFdU), and the novel compound fluorocyclopentenylcytosine (RX3117). DNA was degraded to its deoxynucleotides for quantification by LC-MS-MS, gradient chromatography on a Phenomenex prodigy-3-ODS with positive ionization...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27906459/integrative-genomic-analysis-identifies-ancestry-related-expression-quantitative-trait-loci-on-dna-polymerase-%C3%AE-and-supports-the-association-of-genetic-ancestry-with-survival-disparities-in-head-and-neck-squamous-cell-carcinoma
#10
Meganathan P Ramakodi, Karthik Devarajan, Elizabeth Blackman, Denise Gibbs, Danièle Luce, Jacqueline Deloumeaux, Suzy Duflo, Jeffrey C Liu, Ranee Mehra, Rob J Kulathinal, Camille C Ragin
BACKGROUND: African Americans with head and neck squamous cell carcinoma (HNSCC) have a lower survival rate than whites. This study investigated the functional importance of ancestry-informative single-nucleotide polymorphisms (SNPs) in HNSCC and also examined the effect of functionally important genetic elements on racial disparities in HNSCC survival. METHODS: Ancestry-informative SNPs, RNA sequencing, methylation, and copy number variation data for 316 oral cavity and laryngeal cancer patients were analyzed across 178 DNA repair genes...
December 1, 2016: Cancer
https://www.readbyqxmd.com/read/27902932/adenosine-triphosphate-analogs-can-efficiently-inhibit-the-zika-virus-rna-dependent-rna-polymerase
#11
Kamil Hercík, Jaroslav Kozak, Michal Šála, Milan Dejmek, Hubert Hřebabecký, Eva Zborníková, Miroslav Smola, Daniel Ruzek, Radim Nencka, Evzen Boura
We describe the expression and purification of an active recombinant Zika virus RNA-dependent RNA polymerase (RdRp). Next, we present the development and optimization of an in vitro assay to measure its activity. We then applied the assay to selected triphosphate analogs and discovered that 2'-C-methylated nucleosides exhibit strong inhibitory activity. Surprisingly, also carbocyclic derivatives with the carbohydrate locked in a North-like conformation as well as a ribonucleotide with a South conformation exhibited strong activity...
November 27, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27902775/determinants-of-trna-recognition-by-the-radical-sam-enzyme-rlmn
#12
Christina M Fitzsimmons, Danica Galonić Fujimori
RlmN, a bacterial radical SAM methylating enzyme, has the unusual ability to modify two distinct types of RNA: 23S rRNA and tRNA. In rRNA, RlmN installs a methyl group at the C2 position of A2503 of 23S rRNA, while in tRNA the modification occurs at nucleotide A37, immediately adjacent to the anticodon triplet. Intriguingly, only a subset of tRNAs that contain an adenosine at position 37 are substrates for RlmN, suggesting that the enzyme carefully probes the highly conserved tRNA fold and sequence features to identify its targets...
2016: PloS One
https://www.readbyqxmd.com/read/27902763/temperature-shift-alters-dna-methylation-and-histone-modification-patterns-in-gonadal-aromatase-cyp19a1-gene-in-species-with-temperature-dependent-sex-determination
#13
Yuiko Matsumoto, Brette Hannigan, David Crews
The environment surrounding the embryos has a profound impact on the developmental process and phenotypic outcomes of the organism. In species with temperature-dependent sex determination, gonadal sex is determined by the incubation temperature of the eggs. A mechanistic link between temperature and transcriptional regulation of developmental genes, however, remains elusive. In this study, we examine the changes in DNA methylation and histone modification patterns of the aromatase (cyp19a1) gene in embryonic gonads of red-eared slider turtles (Trachemys scripta) subjected to a temperature shift during development...
2016: PloS One
https://www.readbyqxmd.com/read/27900031/chromosome-16q-genes-cdh1-cdh13-and-adamts18-are-correlated-and-frequently-methylated-in-human-lymphoma
#14
Lobna Alkebsi, Hiroshi Handa, Akihiko Yokohama, Takayuki Saitoh, Norifumi Tsukamoto, Hirokazu Murakami
The products of the E-cadherin (CDH1), H-cadherin (CDH13) and a disintegrin and metalloproteinase with thrombospondin motif 18 (ADAMTS18) genes are proteins displaying structural features and functions on the cell surface membrane, and have been reported to be involved in cancer progression. Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and methylation-specific PCR (MSP) analysis, the promoter methylation status and messenger RNA (mRNA) expression levels of CDH1, CDH13 and ADAMTS18, which are putative tumor-suppressor genes located on chromosome 16q, were evaluated...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899658/the-big-data-center-from-deposition-to-integration-to-translation
#15
(no author information available yet)
Biological data are generated at unprecedentedly exponential rates, posing considerable challenges in big data deposition, integration and translation. The BIG Data Center, established at Beijing Institute of Genomics (BIG), Chinese Academy of Sciences, provides a suite of database resources, including (i) Genome Sequence Archive, a data repository specialized for archiving raw sequence reads, (ii) Gene Expression Nebulas, a data portal of gene expression profiles based entirely on RNA-Seq data, (iii) Genome Variation Map, a comprehensive collection of genome variations for featured species, (iv) Genome Warehouse, a centralized resource housing genome-scale data with particular focus on economically important animals and plants, (v) Methylation Bank, an integrated database of whole-genome single-base resolution methylomes and (vi) Science Wikis, a central access point for biological wikis developed for community annotations...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899423/myc-mediates-mrna-cap-methylation-of-canonical-wnt-beta-catenin-signaling-transcripts-by-recruiting-cdk7-and-rna-methyltransferase
#16
Valeriya Posternak, Matthew H Ung, Chao Cheng, Michael D Cole
: MYC is a pleiotropic transcription factor that activates and represses a wide range of target genes and is frequently deregulated in human tumors. While much is known about the role of MYC in transcriptional activation and repression, MYC can also regulate mRNA cap methylation through a mechanism that has remained poorly understood. Here it is reported that MYC enhances mRNA cap methylation of transcripts globally, specifically increasing mRNA cap methylation of genes involved in Wnt/beta-catenin signaling...
November 29, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27896396/metabolic-profiling-of-ob-ob-mouse-fatty-liver-using-hr-mas-1-h-nmr-combined-with-gene-expression-analysis-reveals-alterations-in-betaine-metabolism-and-the-transsulfuration-pathway
#17
Mikheil Gogiashvili, Karolina Edlund, Kathrin Gianmoena, Rosemarie Marchan, Alexander Brik, Jan T Andersson, Jörg Lambert, Katrin Madjar, Birte Hellwig, Jörg Rahnenführer, Jan G Hengstler, Roland Hergenröder, Cristina Cadenas
Metabolic perturbations resulting from excessive hepatic fat accumulation are poorly understood. Thus, in this study, leptin-deficient ob/ob mice, a mouse model of fatty liver disease, were used to investigate metabolic alterations in more detail. Metabolites were quantified in intact liver tissues of ob/ob (n = 8) and control (n = 8) mice using high-resolution magic angle spinning (HR-MAS) (1)H-NMR. In addition, after demonstrating that HR-MAS (1)H-NMR does not affect RNA integrity, transcriptional changes were measured by quantitative real-time PCR on RNA extracted from the same specimens after HR-MAS (1)H-NMR measurements...
November 28, 2016: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/27893851/expression-and-regulation-of-piwil-proteins-and-piwi-interacting-rnas-in-rheumatoid-arthritis
#18
Lenka Pleštilová, Michel Neidhart, Giancarlo Russo, Mojca Frank-Bertoncelj, Caroline Ospelt, Adrian Ciurea, Christoph Kolling, Renate E Gay, Beat A Michel, Jiří Vencovský, Steffen Gay, Astrid Jüngel
OBJECTIVE: The PIWIL (P-element induced wimpy testis like protein) subfamily of argonaute proteins is essential for Piwi-interacting RNA (piRNA) biogenesis and their function to silence transposons during germ-line development. Here we explored their presence and regulation in rheumatoid arthritis (RA). METHODS: The expression of PIWIL genes in RA and osteoarthritis (OA) synovial tissues and synovial fibroblasts (SF) was analysed by Real-time PCR, immunofluorescence and Western blot...
2016: PloS One
https://www.readbyqxmd.com/read/27892767/epigenetic-modifications-in-multiple-myeloma-recent-advances-on-the-role-of-dna-and-histone-methylation
#19
Nicola Amodio, Patrizia D'Aquila, Giuseppe Passarino, Pierfrancesco Tassone, Dina Bellizzi
Multiple Myeloma (MM) is a clonal late B-cell disorder accounting for about 13% of hematological cancers and 1% of all neoplastic diseases. Recent studies on the molecular pathogenesis and biology of MM have highlighted a complex epigenomic landscape contributing to MM onset, prognosis and high individual variability. Areas covered: We describe here the current knowledge on epigenetic events characterizing MM initiation and progression, focusing on the role of DNA and histone methylation and on the most promising epi-therapeutic approaches targeting the methylation pathway...
November 28, 2016: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/27892455/selective-suppression-of-antisense-transcription-by-set2-mediated-h3k36-methylation
#20
Swaminathan Venkatesh, Hua Li, Madelaine M Gogol, Jerry L Workman
Maintenance of a regular chromatin structure over the coding regions of genes occurs co-transcriptionally via the 'chromatin resetting' pathway. One of the central players in this pathway is the histone methyltransferase Set2. Here we show that the loss of Set2 in yeast, Saccharomyces cerevisiae, results in transcription initiation of antisense RNAs embedded within body of protein-coding genes. These RNAs are distinct from the previously identified non-coding RNAs and cover 11% of the yeast genome. These RNA species have been named Set2-repressed antisense transcripts (SRATs) since the co-transcriptional addition of the H3K36 methyl mark by Set2 over their start sites results in their suppression...
November 28, 2016: Nature Communications
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