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https://www.readbyqxmd.com/read/28441492/caenorhabditis-elegans-prmt-7-and-prmt-9-are-evolutionarily-conserved-protein-arginine-methyltransferases-with-distinct-substrate-specificities
#1
Andrea Hadjikyriacou, Steven Gerard Clarke
Caenorhabditis elegans protein arginine methyltransferases PRMT-7 and PRMT-9 are two evolutionarily conserved enzymes, with distinct orthologs in plants, invertebrates, and vertebrates. Biochemical characterization of these two enzymes reveals that they share much in common with their mammalian orthologs. C. elegans PRMT-7 produces only monomethyl arginine (MMA) and preferentially methylates R-X-R motifs in a broad collection of substrates, including human histone peptides and RG-rich peptides. In addition, the activity of the PRMT-7 enzyme is dependent on temperature, the presence of metal ions, and the reducing agent dithiothreitol (DTT)...
April 25, 2017: Biochemistry
https://www.readbyqxmd.com/read/28441426/identification-of-genes-associated-with-dissociation-of-cognitive-performance-and-neuropathological-burden-multistep-analysis-of-genetic-epigenetic-and-transcriptional-data
#2
Charles C White, Hyun-Sik Yang, Lei Yu, Lori B Chibnik, Robert J Dawe, Jingyun Yang, Hans-Ulrich Klein, Daniel Felsky, Alfredo Ramos-Miguel, Konstantinos Arfanakis, William G Honer, Reisa A Sperling, Julie A Schneider, David A Bennett, Philip L De Jager
INTRODUCTION: The molecular underpinnings of the dissociation of cognitive performance and neuropathological burden are poorly understood, and there are currently no known genetic or epigenetic determinants of the dissociation. METHODS AND FINDINGS: "Residual cognition" was quantified by regressing out the effects of cerebral pathologies and demographic characteristics on global cognitive performance proximate to death. To identify genes influencing residual cognition, we leveraged neuropathological, genetic, epigenetic, and transcriptional data available for deceased participants of the Religious Orders Study (n = 492) and the Rush Memory and Aging Project (n = 487)...
April 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28440828/synthesis-duplex-forming-ability-enzymatic-stability-and-in-vitro-antisense-potency-of-oligonucleotides-including-2-c-4-c-ethyleneoxy-bridged-thymidine-derivatives
#3
Takashi Osawa, Motoki Sawamura, Fumito Wada, Tsuyoshi Yamamoto, Satoshi Obika, Yoshiyuki Hari
We synthesized thymidine derivatives of 2'-C,4'-C-ethyleneoxy-bridged 2'-deoxyribonucleic acids with an 8'-methyl group ((R)-Me-EoDNA and (S)-Me-EoDNA) and without any substituent (EoDNA). Oligonucleotides including these EoDNAs showed high hybridization abilities with complementary RNA and excellent enzymatic stabilities compared with natural DNA. Moreover, the in vitro antisense potency of oligonucleotides with these EoDNAs and our recently reported methylene-EoDNAs was investigated and compared with that of LNA, which is a practical chemical modification for oligonucleotide-therapeutic agents...
April 25, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28440690/the-chemistries-and-consequences-of-dna-and-rna-methylation-and-demethylation
#4
Franziska R Traube, Thomas Carell
No abstract text is available yet for this article.
April 25, 2017: RNA Biology
https://www.readbyqxmd.com/read/28440495/relationship-between-epigenetic-changes-in-wnt-antagonists-and-acute-leukemia
#5
Hua-Rong Zhou, Hai-Ying Fu, Dan-Sen Wu, Yuan-Yuan Zhang, Si-Han Huang, Cong-Jie Chen, Jian-Guo Yan, Jin-Long Huang, Jian-Zhen Shen
The present study was designed to investigate the relationship among epigenetic changes in Wnt antagonists, histone H4K20me1 and the expression of tumor-suppressor genes in acute leukemia (AL) to better understand the pathogenesis of leukemia. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to detect messenger RNA (mRNA) expression levels of Wnt antagonists (Wnt5a, HDPR1, DKK1 and DKK3) in patients with AL and in normal controls; pyrophosphate sequencing was performed to detect the methylation status of the Wnt5a promoter; and western blotting was performed to detect the overall expression levels of Wnt5a protein and histone H4K20me1 in patients with acute myeloid leukemia (AML) and in normal controls...
May 2017: Oncology Reports
https://www.readbyqxmd.com/read/28440291/identifying-n-6-methyladenosine-sites-using-multi-interval-nucleotide-pair-position-specificity-and-support-vector-machine
#6
Pengwei Xing, Ran Su, Fei Guo, Leyi Wei
N6-methyladenosine (m(6)A) refers to methylation of the adenosine nucleotide acid at the nitrogen-6 position. It plays an important role in a series of biological processes, such as splicing events, mRNA exporting, nascent mRNA synthesis, nuclear translocation and translation process. Numerous experiments have been done to successfully characterize m(6)A sites within sequences since high-resolution mapping of m(6)A sites was established. However, as the explosive growth of genomic sequences, using experimental methods to identify m(6)A sites are time-consuming and expensive...
April 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28439401/long-non-coding-rna-malat1-contributes-to-cell-apoptosis-by-sponging-mir-124-in-parkinson-disease
#7
Wei Liu, Qishun Zhang, Jianlei Zhang, Wujun Pan, Jingya Zhao, Yuming Xu
BACKGROUND: Parkinson disease (PD) is the most common movement disturbance characterized by the loss of dopaminergic (DA) neurons in midbrain. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is aberrantly expressed in neurons and is involved in the dendritic and synapse development. However, the role of MALAT1 and its underlying mechanism in PD remain to be defined. METHODS: The expressions of MALAT1 and miR-124 were evaluated by qRT-PCR. N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice and SH-SY5Y cells subjected to N-methyl-4-phenylpyridinium (MPP(+)) were utilized to investigate the effect of MALAT1 on PD...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/28439102/mecp2-regulated-mirnas-control-early-human-neurogenesis-through-differential-effects-on-erk-and-akt-signaling
#8
N Mellios, D A Feldman, S D Sheridan, J P K Ip, S Kwok, S K Amoah, B Rosen, B A Rodriguez, B Crawford, R Swaminathan, S Chou, Y Li, M Ziats, C Ernst, R Jaenisch, S J Haggarty, M Sur
Rett syndrome (RTT) is an X-linked, neurodevelopmental disorder caused primarily by mutations in the methyl-CpG-binding protein 2 (MECP2) gene, which encodes a multifunctional epigenetic regulator with known links to a wide spectrum of neuropsychiatric disorders. Although postnatal functions of MeCP2 have been thoroughly investigated, its role in prenatal brain development remains poorly understood. Given the well-established importance of microRNAs (miRNAs) in neurogenesis, we employed isogenic human RTT patient-derived induced pluripotent stem cell (iPSC) and MeCP2 short hairpin RNA knockdown approaches to identify novel MeCP2-regulated miRNAs enriched during early human neuronal development...
April 25, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28439098/uncoupling-dapk1-from-nmda-receptor-glun2b-subunit-exerts-rapid-antidepressant-like-effects
#9
S-X Li, Y Han, L-Z Xu, K Yuan, R-X Zhang, C-Y Sun, D-F Xu, M Yuan, J-H Deng, S-Q Meng, X-J Gao, Q Wen, L-J Liu, W-L Zhu, Y-X Xue, M Zhao, J Shi, L Lu
Several preclinical studies have reported the rapid antidepressant effects of N-methyl-D-aspartate receptor (NMDAR) antagonists, although the underlying mechanisms are still unclear. Death-associated protein kinase 1 (DAPK1) couples GluN2B subunits at extrasynaptic sites to regulate NMDAR channel conductance. In the present study, we found that chronic unpredictable stress (CUS) induced extracellular glutamate accumulation, accompanied by an increase in the DAPK1-NMDAR interaction, the high expression of DAPK1 and phosphorylated GluN2B at Ser1303, a decrease in phosphorylated DAPK1 at Ser308 and synaptic protein deficits in the rat medial prefrontal cortex (mPFC)...
April 25, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28433859/photoelectrochemical-immunosensor-for-methylated-rna-detection-based-on-g-c3n4-cds-quantum-dots-heterojunction-and-phos-tag-biotin
#10
Haiyan Wang, Qihai Zhang, Huanshun Yin, Minghui Wang, Wenjing Jiang, Shiyun Ai
N(6)-methyladenosine (m(6)A) is an enigmatic and abundant internal modification in eukaryotic messenger RNA (mRNA), which could affect various aspects of RNA metabolism and mRNA translation. Herein, a novel photoelectrochemical (PEC) immunosensor was constructed for m(6)A detection based on the inhibition of Cu(2+) to the photoactivity of g-C3N4/CdS quantum dots (g-C3N4/CdS) heterojunction, where g-C3N4/CdS heterojunction was used as photoactive material, anti-m(6)A antibody as recognition unit for m(6)A-containing RNA, Phos-tag-biotin as link unit and avidin functionalized CuO as PEC signal indicator...
April 12, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28433422/postnatal-choline-supplementation-selectively-attenuates-hippocampal-microrna-alterations-associated-with-developmental-alcohol-exposure
#11
Sridevi Balaraman, Nirelia M Idrus, Rajesh C Miranda, Jennifer D Thomas
Prenatal alcohol exposure can result in a range of physical, neuropathological, and behavioral alterations, collectively termed fetal alcohol spectrum disorders (FASD). We have shown that supplementation with the nutrient choline reduces the severity of developmental alcohol-associated deficits in hippocampal-dependent behaviors and normalizes some aspects of hippocampal cholinergic development and DNA methylation patterns. Alcohol's developmental effects may also be mediated, in part, by altering microRNAs (miRNAs) that serve as negative regulators of gene translation...
January 3, 2017: Alcohol
https://www.readbyqxmd.com/read/28432622/diversity-shift-in-bacterial-phenol-hydroxylases-driven-by-alkyl-phenols-in-oil-refinery-wastewaters
#12
Besma Harzallah, Hacène Bousseboua, Yves Jouanneau
Phenol hydroxylases (PHs) play a primary role in the bacterial degradation of phenol and alkylphenols. They are divided into two main classes, single-component and multi-component PHs, having distinctive catalytic subunits designated as PheA1 and LmPH, respectively. The diversity of these enzymes is still largely unexplored. Here, both LmPH and pheA1 gene sequences were examined in activated sludge from oil refinery wastewaters. Phenol, p-cresol, or 3,4-dimethylphenol (3,4-DMP) supplied as extra carbon sources were rapidly mineralized by the microbial community...
April 21, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28430172/ezh2-alterations-in-follicular-lymphoma-biological-and-clinical-correlations
#13
S Huet, L Xerri, B Tesson, S Mareschal, S Taix, L Mescam-Mancini, E Sohier, M Carrère, J Lazarovici, O Casasnovas, L Tonon, S Boyault, S Hayette, C Haioun, B Fabiani, A Viari, F Jardin, G Salles
The histone methyltransferase EZH2 has an essential role in the development of follicular lymphoma (FL). Recurrent gain-of-function mutations in EZH2 have been described in 25% of FL patients and induce aberrant methylation of histone H3 lysine 27 (H3K27). We evaluated the role of EZH2 genomic gains in FL biology. Using RNA sequencing, Sanger sequencing and SNP-arrays, the mutation status, copy-number and gene-expression profiles of EZH2 were assessed in a cohort of 159 FL patients from the PRIMA trial. Immunohistochemical (IHC) EZH2 expression (n=55) and H3K27 methylation (n=63) profiles were also evaluated...
April 21, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28428565/small-methyltransferase-rlmh-assembles-a-composite-active-site-to-methylate-a-ribosomal-pseudouridine
#14
Cha San Koh, Rohini Madireddy, Timothy J Beane, Phillip D Zamore, Andrei A Korostelev
Eubacterial ribosomal large-subunit methyltransferase H (RlmH) methylates 23S ribosomal RNA pseudouridine 1915 (Ψ1915), which lies near the ribosomal decoding center. The smallest member of the SPOUT superfamily of methyltransferases, RlmH lacks the RNA recognition domain found in larger methyltransferases. The catalytic mechanism of RlmH enzyme is unknown. Here, we describe the structures of RlmH bound to S-adenosyl-methionine (SAM) and the methyltransferase inhibitor sinefungin. Our structural and biochemical studies reveal catalytically essential residues in the dimer-mediated asymmetrical active site...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428443/mechanisms-of-pinometostat-epz-5676-treatment-emergent-resistance-in-mll-rearranged-leukemia
#15
Carly T Campbell, Jessica N Haladyna, David A Drubin, Ty M Thomson, Michael J Maria, Taylor Yamauchi, Nigel J Waters, Edward J Olhava, Roy M Pollock, Jesse J Smith, Robert A Copeland, Stephen J Blakemore, Kathrin M Bernt, Scott R Daigle
DOT1L is a protein methyltransferase involved in the development and maintenance of MLL-rearranged (MLL-r) leukemia through its ectopic methylation of histones associated with well characterized leukemic genes.  Pinometostat (EPZ-5676), a selective inhibitor of DOT1L, is in clinical development in relapsed/refractory acute leukemia patients harboring rearrangements of the MLL gene. The observation of responses and subsequent relapses in the adult trial treating MLL-r patients motivated preclinical investigations into potential mechanisms of pinometostat treatment emergent resistance (TER) in cell lines confirmed to have MLL-r...
April 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28428215/blocked-transcription-through-kvdmr1-results-in-absence-of-methylation-and-gene-silencing-resembling-beckwith-wiedemann-syndrome
#16
Vir B Singh, Sirinapa Sribenja, Kayla E Wilson, Kristopher M Attwood, Joanna C Hillman, Shilpa Pathak, Michael J Higgins
The maternally methylated KvDMR1 ICR regulates imprinted expression of a cluster of maternally-expressed genes on human chromosome 11p15.5. Disruption of imprinting leads to Beckwith-Wiedemann syndrome (BWS), an overgrowth and cancer predisposition condition. In the majority of BWS patients, maternal-specific methylation at KvDMR1 is absent and genes under its control are repressed. We analyzed a mouse model carrying a poly(A) truncation cassette inserted to prevent RNA transcripts from elongation through KvDMR1...
April 20, 2017: Development
https://www.readbyqxmd.com/read/28427179/comprehensive-mapping-of-the-effects-of-azacitidine-on-dna-methylation-repressive-permissive-histone-marks-and-gene-expression-in-primary-cells-from-patients-with-mds-and-mds-related-disease
#17
Magnus Tobiasson, Hani Abdulkadir, Andreas Lennartsson, Shintaro Katayama, Francesco Marabita, Ayla De Paepe, Mohsen Karimi, Kaarel Krjutskov, Elisabet Einarsdottir, Michael Grövdal, Monika Jansson, Asmaa Ben Azenkoud, Lina Corddedu, Sören Lehmann, Karl Ekwall, Juha Kere, Eva Hellström-Lindberg, Johanna Ungerstedt
Azacitidine (Aza) is first-line treatment for patients with high-risk myelodysplastic syndromes (MDS), although its precise mechanism of action is unknown. We performed the first study to globally evaluate the epigenetic effects of Aza on MDS bone marrow progenitor cells assessing gene expression (RNA seq), DNA methylation (Illumina 450k) and the histone modifications H3K18ac and H3K9me3 (ChIP seq). Aza induced a general increase in gene expression with 924 significantly upregulated genes but this increase showed no correlation with changes in DNA methylation or H3K18ac, and only a weak association with changes in H3K9me3...
February 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28425161/atorvastatin-treatment-modulates-p16-promoter-methylation-to-regulate-p16-expression
#18
Boqian Zhu, Yaoyao Gong, Gaoliang Yan, Dong Wang, Qingjie Wang, Yong Qiao, Jiantong Hou, Bo Liu, Chengchun Tang
Intimal hyperplasia, the key event of artery restenosis, was a result of cell proliferation and cell migration. Atorvastatin experts an inhibitory effect on cell proliferation and migration but its mechanism remains largely unknown. p16, as a well-known tumor suppressor, was also reported to suppress cell growth and migration, but with vague mechanism. In this study, we demonstrated atorvastatin represses cell proliferation and migration in vascular smooth muscle cells (VSMCs), which process is mediated by p16...
April 20, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28424740/essential-role-of-long-non-coding-rnas-in-de-novo-chromatin-modifications-the-genomic-address-code-hypothesis
#19
Ken Nishikawa, Akira R Kinjo
The epigenome, i.e., the whole of chromatin modifications, is transferred from mother to daughter cells during cell differentiation. When de novo chromatin modifications (establishment or erasure of, respectively, new or pre-existing DNA methylations and/or histone modifications) are made in a daughter cell, however, it has a different epigenome than its mother cell. Although de novo chromatin modification is an important event that comprises elementary processes of cell differentiation, its molecular mechanism remains poorly understood...
April 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/28424484/the-tandem-agenet-domain-of-fragile-x-mental-retardation-protein-interacts-with-fus
#20
Qingzhong He, Wei Ge
The tandem Agenet domain (TAD) of fragile X mental retardation protein (FMRP) protein is considered to be a member of the methyl-lysine-binding Tudor domain "Royal family". Several groups have reported that the TAD binds with methylated histones and plays a role in DNA damage responses. FMRP is a RNA-binding protein predominantly resident in cytoplasm. Therefore, in this study, we identified DDX5, FUS, EWSR1 and LSM14A as TAD-interacting proteins sensitive to F32L and/or Y96L mutation by pull-down assays and mass spectrometry...
April 19, 2017: Scientific Reports
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