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RNA methylation

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https://www.readbyqxmd.com/read/28107630/2-o-methyl-5-hydroxymethylcytidine-a-second-oxidative-derivative-of-5-methylcytidine-in-rna
#1
Sabrina M Huber, Pieter van Delft, Arun A Tanpure, Eric A Miska, Shankar Balasubramanian
5-hydroxymethylcytidine (hm5C) was recently identified as a direct metabolite of m5C in RNA. We investigated the stability of hm5C in human cells using bio-isotopomers and high-resolution tandem LC-MS/MS. This has led to the discovery of a second oxidative metabolite of m5C in RNA, namely 2'-O-methyl-5-hydroxymethylcytidine (hm5Cm). Subsequent quantitative analysis of total RNA from higher organisms, revealed varying levels and TET-independent formation of this new RNA modification.
January 20, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28107589/serum-lincrna-p21-as-a-potential-biomarker-of-liver-fibrosis-in-chronic-hepatitis-b-patients
#2
Fujun Yu, Guangyao Zhou, Kate Huang, XuFei Fan, Guojun Li, Bicheng Chen, Peihong Dong, Jianjian Zheng
Serum long non-coding RNAs (lncRNAs) are emerging as promising biomarkers for various human diseases. The aim of this study was to investigate the feasibility of using serum long intergenic non-coding RNA-p21 (lincRNA-p21) as a biomarker for chronic hepatitis B patients. Serum lincRNA-p21 levels were quantified using real-time PCR in 417 CHB patients and 363 healthy controls. The promoter methylation level of lincRNA-p21 was detected using bisulfite-sequencing analysis in primary hepatic stellate cells (HSCs)...
January 20, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28106072/ythdf3-facilitates-translation-and-decay-of-n-6-methyladenosine-modified-rna
#3
Hailing Shi, Xiao Wang, Zhike Lu, Boxuan S Zhao, Honghui Ma, Phillip J Hsu, Chuan He
N(6)-methyladenosine (m(6)A) is the most abundant internal modification in eukaryotic messenger RNAs (mRNAs), and plays important roles in cell differentiation and tissue development. It regulates multiple steps throughout the RNA life cycle including RNA processing, translation, and decay, via the recognition by selective binding proteins. In the cytoplasm, m(6)A binding protein YTHDF1 facilitates translation of m(6)A-modified mRNAs, and YTHDF2 accelerates the decay of m(6)A-modified transcripts. The biological function of YTHDF3, another cytoplasmic m(6)A binder of the YTH (YT521-B homology) domain family, remains unknown...
January 20, 2017: Cell Research
https://www.readbyqxmd.com/read/28102032/nonpromoter-methylation-of-the-cdkn2a-gene-with-active-transcription-is-associated-with-improved-locoregional-control-in-laryngeal-squamous-cell-carcinoma
#4
Miriam M Ben-Dayan, Thomas J Ow, Thomas J Belbin, Joshua Wetzler, Richard V Smith, Geoffrey Childs, Brenda Diergaarde, D Neil Hayes, Jennifer R Grandis, Michael B Prystowsky, Nicolas F Schlecht
We previously reported a novel association between CDKN2A nonpromoter methylation and transcription (ARF/INK4a) in human papillomavirus associated oropharyngeal tumors. In this study we assessed whether nonpromoter CDKN2A methylation in laryngeal squamous cell carcinomas (LXSCC) conferred a similar association with transcription that predicted patient outcome. We compared DNA methylation and ARF/INK4a RNA expression levels for the CDKN2A locus using the Illumina HumanMethylation27 beadchip and RT-PCR in 43 LXSCC tumor samples collected from a prospective study of head and neck cancer patients treated at Montefiore Medical Center (MMC)...
January 19, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28101966/the-free-energy-of-locking-a-ring-changing-a-deoxyribonucleoside-to-a-locked-nucleic-acid
#5
You Xu, Alessandra Villa, Lennart Nilsson
Locked nucleic acid (LNA), a modified nucleoside which contains a bridging group across the ribose ring, improves the stability of DNA/RNA duplexes significantly, and therefore is of interest in biotechnology and gene therapy applications. In this study, we investigate the free energy change between LNA and DNA nucleosides. The transformation requires the breaking of the bridging group across the ribose ring, a problematic transformation in free energy calculations. To address this, we have developed a 3-step (easy to implement) and a 1-step protocol (more efficient, but more complicated to setup), for single and dual topologies in classical molecular dynamics simulations, using the Bennett Acceptance Ratio method to calculate the free energy...
January 19, 2017: Journal of Computational Chemistry
https://www.readbyqxmd.com/read/28101374/arginine-methylation-of-usp9x-promotes-its-interaction-with-tdrd3-and-its-anti-apoptotic-activities-in-breast-cancer-cells
#6
Nithya Narayanan, Zhihao Wang, Ling Li, Yanzhong Yang
The Tudor domain-containing proteins are characterized by their specific interactions with methylated protein motifs, including methyl-arginines and methyl-lysines. The Tudor domain-containing protein 3 (TDRD3) is one of the major methyl-arginine effector molecules that recognizes methylated arginine residues on histones and the C-terminal domain of RNA polymerase II, and activates transcription. However, majority of the cellular TDRD3 localizes to the cytoplasm and its functions there are still elusive. Here, we have identified ubiquitin-specific protease 9 X-linked (USP9X) as a TDRD3-interacting protein by GST (glutathione S-transferase) pull-down and co-immunoprecipitation...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28101227/downregulation-of-mir-23b-in-plasma-is-associated-with-poor-prognosis-in-patients-with-colorectal-cancer
#7
Chang-Hua Kou, Tian Zhou, Xi-Lin Han, Hui-Jie Zhuang, Hai-Xin Qian
MicroRNAs (miRNAs) are short, non-coding RNA molecules that act as regulators of gene expression. Circulating blood miRNAs have potential as cancer biomarkers. The main objective of the present study was to assess the effect of miRNA-23b (miR-23b) expression in plasma on the diagnosis and prognosis of colorectal cancer (CRC). Reverse transcription-quantitative polymerase chain reaction (PCR) was used to measure miR-23b expression levels, and methylation-specific PCR was used to test the promoter methylation status...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28100749/promoted-interaction-of-c-ebp%C3%AE-with-demethylated-cxcr3-gene-promoter-contributes-to-neuropathic-pain-in-mice
#8
Bao-Chun Jiang, Li-Na He, Xiao-Bo Wu, Hui Shi, Wen-Wen Zhang, Zhi-Jun Zhang, De-Li Cao, Chun-Hua Li, Jun Gu, Yong-Jing Gao
: DNA methylation has been implicated in the pathogenesis of chronic pain. However, the specific genes regulated by DNA methylation under neuropathic pain condition remain largely unknown. Here we investigated how chemokine receptor CXCR3 is regulated by DNA methylation and how it contributes to neuropathic pain induced by spinal nerve ligation (SNL) in mice. SNL increased Cxcr3 mRNA and protein expression in the neurons of the spinal cord. Meanwhile, the CpG (5'-cytosine-phosphate-guanine-3') island in the Cxcr3 gene promoter region was demethylated, and the expression of DNA methyltransferase 3b (DNMT3b) was decreased...
January 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28098555/nematophagous-fungus-arthrobotrys-oligospora-mimics-olfactory-cues-of-sex-and-food-to-lure-its-nematode-prey
#9
Yen-Ping Hsueh, Matthew R Gronquist, Erich M Schwarz, Ravi David Nath, Ching-Han Lee, Shalha Gharib, Frank C Schroeder, Paul W Sternberg
To study the molecular basis for predator-prey coevolution, we investigated how Caenorhabditis elegans responds to the predatory fungus Arthrobotrys oligospora. C. elegans and other nematodes were attracted to volatile compounds produced by A. oligospora. Gas-chromatographic mass-spectral analyses of A. oligospora-derived volatile metabolites identified several odors mimicking food cues attractive to nematodes. One compound, methyl 3-methyl-2-butenoate (MMB) additionally triggered strong sex- and stage-specific attraction in several Caenorhabditis species...
January 18, 2017: ELife
https://www.readbyqxmd.com/read/28097898/two-approaches-to-the-use-of-benzo-c-1-2-oxaboroles-as-active-fragments-for-synthetic-transformation-of-clarithromycin
#10
Gennady B Lapa, Elena P Mirchink, Elena B Isakova, Maria N Preobrazhenskaya
Clarithromycin (active against Gram positive infections) and 1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborole derivatives (effective for Gram negative microbes) are the ligands of bacterial RNA. The antimicrobial activities of these benzoxaboroles linked with clarithromycin at 9 or 4″ position were compared. Two synthetic pathways for these conjugates were elaborated. First pathway explored the substitution of the C-9 carbonyl group of macrolactone's cycle via oxime linker, the second direction used the modification of the 4″-O-group of cladinose via the formation of carbamates of benzoxaboroles...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/28097824/mechanisms-of-metabolic-memory-and-renal-hypoxia-as-a-therapeutic-target-in-diabetic-kidney-disease
#11
REVIEW
Yosuke Hirakawa, Tetsuhiro Tanaka, Masaomi Nangaku
Diabetic kidney disease (DKD) is a worldwide public health problem. The definition of DKD is being under discussion. Although the term DKD was originally defined as "kidney disease specific to diabetes", DKD frequently means chronic kidney disease (CKD) with diabetes mellitus and includes not only classical diabetic nephropathy, but also kidney dysfunction due to nephrosclerosis and other causes. Metabolic memory plays a crucial role in the progression of various complications of diabetes, including DKD. The mechanisms of metabolic memory in DKD are supposed to include advanced glycation end products, DNA methylation, histone modifications, and non-coding RNA including microRNA...
January 17, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28096468/o-glcnac-expression-levels-epigenetically-regulate-colon-cancer-tumorigenesis-by-affecting-the-cancer-stem-cell-compartment-via-modulating-expression-of-transcriptional-factor-mybl1
#12
Huabei Guo, Bing Zhang, Alison V Nairn, Tamas Nagy, Kelley W Moremen, Phillip Buckhaults, Michael Pierce
To study the regulation of colorectal adenocarcinoma progression by O-GlcNAc, we have focused on the O-GlcNAc-mediated epigenetic regulation of human colon cancer stem cells (CCSC). Xenograft tumors from colon tumor cells with OGT knockdown grew significantly slower than those formed from control cells, indicating a reduced proliferation of tumor cells due to inhibition of OGT expression. Significant reduction of CCSC population was observed in the tumor cells after OGT knockdown, while tumor cells treated with O-GlcNAcase inhibitor showed an increased CCSC population, indicating that O-GlcNAc levels regulated the CCSC compartment...
January 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28094554/impact-of-phytochemicals-and-dietary-patterns-on-epigenome-and-cancer
#13
Wissam Zam, Aziz Khadour
Cancer remains one of the leading causes of death around the world. Initially it is recognized as a genetic disease, but now it is known to involve epigenetic abnormalities along with genetic alterations. Epigenetics refers to heritable changes that are not encoded in the DNA sequence itself, but play an important role in the control of gene expression. It includes changes in DNA methylation, histone modifications, and RNA interference. Although it is heritable, environmental factors such as diet could directly influence epigenetic mechanisms in humans...
January 17, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/28093925/hypermethylation-of-antisense-long-noncoding-rnas-in-acute-lymphoblastic-leukemia
#14
Gerald Arthur, Md Almamun, Kristen Taylor
AIM: Long noncoding RNAs serve critical regulatory functions highly specific for a tissue and its developmental stage. Antisense long ncRNA (AS-lncRNA) methylation changes in acute lymphoblastic leukemia (ALL) versus normal pre-B-cell lymphoblasts were evaluated to identify potential differential methylation in this group of genes. MATERIALS & METHODS: The methylome of ALL and normal lymphoblasts was examined by the methylated CpG island recovery assay followed by NGS...
January 17, 2017: Epigenomics
https://www.readbyqxmd.com/read/28093566/estrogen-dependent-association-of-hdac4-with-fear-in-female-mice-and-women-with-ptsd
#15
S A Maddox, V Kilaru, J Shin, T Jovanovic, L M Almli, B G Dias, S D Norrholm, N Fani, V Michopoulos, Z Ding, K N Conneely, E B Binder, K J Ressler, A K Smith
Women are at increased risk of developing post-traumatic stress disorder (PTSD) following a traumatic event. Recent studies suggest that this may be mediated, in part, by circulating estrogen levels. This study evaluated the hypothesis that individual variation in response to estrogen levels contributes to fear regulation and PTSD risk in women. We evaluated DNA methylation from blood of female participants in the Grady Trauma Project and found that serum estradiol levels associates with DNA methylation across the genome...
January 17, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28093071/spag6-and-l1td1-are-transcriptionally-regulated-by-dna-methylation-in-non-small-cell-lung-cancers
#16
Corinna Altenberger, Gerwin Heller, Barbara Ziegler, Erwin Tomasich, Maximilian Marhold, Thais Topakian, Leonhard Müllauer, Petra Heffeter, György Lang, Adelheid End-Pfützenreuter, Balazs Döme, Britt-Madeleine Arns, Walter Klepetko, Christoph C Zielinski, Sabine Zöchbauer-Müller
BACKGROUND: DNA methylation regulates together with other epigenetic mechanisms the transcriptional activity of genes and is involved in the pathogenesis of malignant diseases including lung cancer. In non-small cell lung cancer (NSCLC) various tumor suppressor genes are already known to be tumor-specifically methylated. However, from the vast majority of a large number of genes which were identified to be tumor-specifically methylated, tumor-specific methylation was unknown so far. Thus, the major aim of this study was to investigate in detail the mechanism(s) responsible for transcriptional regulation of the genes SPAG6 and L1TD1 in NSCLCs...
January 5, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28091876/hypermethylation-of-ifn-%C3%AE-in-oral-cancer-tissues
#17
Songbo Tian, Chunyang Jiang, Xiaoqin Liu, Sheng Xu, Zhiyong Zhang, Huizhen Chen, Yinghuai Zhang, Yanping Liu, Dong Ma
OBJECTIVES: The study aimed to evaluate the methylation pattern of the interferon-gamma (IFN-γ) gene in oral cancer tissues compared with normal and benign oral disease tissues. MATERIALS AND METHODS: The oral tissues were gained from the patients of 85 cases of oral squamous cell carcinoma (OSCC), 47 cases of oral dysplastic lesions, and 53 normal biopsies. IFN -γ methylation in oral tissues was verified through methylation-specific polymerase chain reaction (PCR) and DNA sequencing analyses, and the expression levels of IFN-γ messenger RNA (mRNA) and protein were detected using real-time reverse transcription (RT)-PCR and enzyme-linked immunosorbent assays, respectively...
January 13, 2017: Clinical Oral Investigations
https://www.readbyqxmd.com/read/28091672/a-rapid-way-to-discover-nonstandard-macrocyclic-peptide-modulators-of-drug-targets
#18
Toby Passioura, Hiroaki Suga
Studies of the fundamental nature of RNA catalysis and the potential mechanism of a shift from the "RNA world" to proteinaceous life lead us to identify a set of ribozymes (flexizymes) capable of promiscuous tRNA acylation. Whilst theoretically and mechanistically interesting in their own right, flexizymes have turned out to have immense practical value for the simple synthesis of tRNAs acylated with unusual amino acids, which in turn can be used for the ribosomal synthesis of peptides containing non-canonical residues...
January 16, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28090296/endotoxin-and-mechanical-stress-induced-epigenetic-changes-in-the-regulation-of-the-nicotinamide-phosphoribosyltransferase-promoter
#19
Venkateswaran Ramamoorthi Elangovan, Sara M Camp, Gabriel T Kelly, Ankit A Desai, Djanybek Adyshev, Xiaoguang Sun, Stephen M Black, Ting Wang, Joe G N Garcia
Mechanical ventilation, a lifesaving intervention for patients with acute respiratory distress syndrome (ARDS), also unfortunately contributes to excessive mechanical stress and impaired lung physiological and structural integrity. We have elsewhere established the pivotal role of increased nicotinamide phosphoribosyltransferase (NAMPT) transcription and secretion as well as its direct binding to the toll-like receptor 4 (TLR4) in the progression of this devastating syndrome; however, regulation of this critical gene in ventilator-induced lung injury (VILI) is not well characterized...
December 2016: Pulmonary Circulation
https://www.readbyqxmd.com/read/28089370/single-cell-multiomics-multiple-measurements-from-single-cells
#20
REVIEW
Iain C Macaulay, Chris P Ponting, Thierry Voet
Single-cell sequencing provides information that is not confounded by genotypic or phenotypic heterogeneity of bulk samples. Sequencing of one molecular type (RNA, methylated DNA or open chromatin) in a single cell, furthermore, provides insights into the cell's phenotype and links to its genotype. Nevertheless, only by taking measurements of these phenotypes and genotypes from the same single cells can such inferences be made unambiguously. In this review, we survey the first experimental approaches that assay, in parallel, multiple molecular types from the same single cell, before considering the challenges and opportunities afforded by these and future technologies...
January 12, 2017: Trends in Genetics: TIG
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