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RNA Polymerase II

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https://www.readbyqxmd.com/read/28334904/genome-wide-mapping-of-infection-induced-sine-rnas-reveals-a-role-in-selective-mrna-export
#1
John Karijolich, Yang Zhao, Ravi Alla, Britt Glaunsinger
Short interspersed nuclear elements (SINEs) are retrotransposons evolutionarily derived from endogenous RNA Polymerase III RNAs. Though SINE elements have undergone exaptation into gene regulatory elements, how transcribed SINE RNA impacts transcriptional and post-transcriptional regulation is largely unknown. This is partly due to a lack of information regarding which of the loci have transcriptional potential. Here, we present an approach (short interspersed nuclear element sequencing, SINE-seq), which selectively profiles RNA Polymerase III-derived SINE RNA, thereby identifying transcriptionally active SINE loci...
March 15, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334877/iron-mediates-catalysis-of-nucleic-acid-processing-enzymes-support-for-fe-ii-as-a-cofactor-before-the-great-oxidation-event
#2
C Denise Okafor, Kathryn A Lanier, Anton S Petrov, Shreyas S Athavale, Jessica C Bowman, Nicholas V Hud, Loren Dean Williams
Life originated in an anoxic, Fe2+-rich environment. We hypothesize that on early Earth, Fe2+ was a ubiquitous cofactor for nucleic acids, with roles in RNA folding and catalysis as well as in processing of nucleic acids by protein enzymes. In this model, Mg2+ replaced Fe2+ as the primary cofactor for nucleic acids in parallel with known metal substitutions of metalloproteins, driven by the Great Oxidation Event. To test predictions of this model, we assay the ability of nucleic acid processing enzymes, including a DNA polymerase, an RNA polymerase and a DNA ligase, to use Fe2+ in place of Mg2+ as a cofactor during catalysis...
March 15, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334749/ctg-repeat-targeting-oligonucleotides-for-down-regulating-huntingtin-expression
#3
Eman M Zaghloul, Olof Gissberg, Pedro M D Moreno, Lee Siggens, Mattias Hällbrink, Anna S Jørgensen, Karl Ekwall, Rula Zain, Jesper Wengel, Karin E Lundin, C I Edvard Smith
Huntington's disease (HD) is a fatal, neurodegenerative disorder in which patients suffer from mobility, psychological and cognitive impairments. Existing therapeutics are only symptomatic and do not significantly alter the disease progression or increase life expectancy. HD is caused by expansion of the CAG trinucleotide repeat region in exon 1 of the Huntingtin gene (HTT), leading to the formation of mutant HTT transcripts (muHTT). The toxic gain-of-function of muHTT protein is a major cause of the disease...
February 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28331082/kaposi-s-sarcoma-associated-herpesvirus-hijacks-rna-polymerase-ii-to-create-a-viral-transcriptional-factory
#4
Christopher Phillip Chen, Yuanzhi Lyu, Frank Chuang, Kazushi Nakano, Chie Izumiya, Di Jin, Mel Campbell, Yoshihiro Izumiya
Locally concentrated nuclear factors ensure efficient binding to the DNA templates, facilitating RNA polymerase II recruitment and frequent reutilization of stable pre-initiation complexes. Here we have uncovered a mechanism for effective viral transcription by focal assembly of RNA polymerase II around KSHV genomes in the host cell nucleus. Using immunofluorescent labeling of latent nuclear antigen (LANA) protein, together with fluorescence in situ RNA hybridization (RNA-FISH) of the intron region of immediate-early transcripts, we visualized active transcription of viral genomes in naturally infected cells...
March 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28329680/major-roles-for-pyrimidine-dimers-nucleotide-excision-repair-and-atr-in-the-alternative-splicing-response-to-uv-irradiation
#5
Manuel J Muñoz, Nicolás Nieto Moreno, Luciana E Giono, Adrián E Cambindo Botto, Gwendal Dujardin, Giulia Bastianello, Stefania Lavore, Antonio Torres-Méndez, Carlos F M Menck, Benjamin J Blencowe, Manuel Irimia, Marco Foiani, Alberto R Kornblihtt
We have previously found that UV irradiation promotes RNA polymerase II (RNAPII) hyperphosphorylation and subsequent changes in alternative splicing (AS). We show now that UV-induced DNA damage is not only necessary but sufficient to trigger the AS response and that photolyase-mediated removal of the most abundant class of pyrimidine dimers (PDs) abrogates the global response to UV. We demonstrate that, in keratinocytes, RNAPII is the target, but not a sensor, of the signaling cascade initiated by PDs. The UV effect is enhanced by inhibition of gap-filling DNA synthesis, the last step in the nucleotide excision repair pathway (NER), and reduced by the absence of XPE, the main NER sensor of PDs...
March 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28327789/prevalence-of-hepatitis-c-virus-and-human-immunodeficiency-virus-in-a-group-of-patients-newly-diagnosed-with-active-tuberculosis-in-porto-alegre-southern-brazil
#6
Cintia Costi, Tarciana Grandi, Maria Laura Halon, Márcia Susana Nunes Silva, Cláudia Maria Dornelles da Silva, Tatiana Schäffer Gregianini, Lia Gonçalves Possuelo, Carla Adriane Jarczewski, Christian Niel, Maria Lucia Rosa Rossetti
BACKGROUND: Porto Alegre is the Brazilian state capital with second highest incidence of tuberculosis (TB) and the highest proportion of people infected with human immunodeficiency virus (HIV) among patients with TB. Hepatitis C virus (HCV) infection increases the risk of anti-TB drug-induced hepatotoxicity, which may result in discontinuation of the therapy. OBJECTIVES: The aim of this study was (i) to estimate prevalence of HCV and HIV in a group of patients newly diagnosed with active TB in a public reference hospital in Porto Alegre and (ii) to compare demographic, behavioural, and clinical characteristics of patients in relation to their HCV infection status...
April 2017: Memórias do Instituto Oswaldo Cruz
https://www.readbyqxmd.com/read/28322300/noncanonical-nf-%C3%AE%C2%BAb-mediates-the-suppressive-effect-of-neutrophil-elastase-on-il-8-cxcl8-by-inducing-nkrf-in-human-airway-smooth-muscle
#7
Shu-Chuan Ho, Sheng-Ming Wu, Po-Hao Feng, Wen-Te Liu, Kuan-Yuan Chen, Hsiao-Chi Chuang, Yao-Fei Chan, Lu-Wei Kuo, Kang-Yun Lee
Neutrophil elastase (NE) suppresses IL-8/CXCL8 in human airway smooth muscle cells (hASM) while stimulating its production in respiratory epithelial cells. This differential effect is mediated by the selective induction of NKRF and dysregulation in chronic inflammatory diseases. We hypothesized that the differential activation of NF-κB subunits confer the opposite effect of NKRF on IL-8/CXCL8 in primary hASM and A549 cells stimulated with NE. The events occurring at the promoters of NKRF and IL-8/CXCL8 were observed by ChIP assays, and the functional role of RelB was confirmed by knockdown and overexpression...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28320505/fine-tuning-of-gene-expression-dynamics-by-the-set2-rpd3s-pathway
#8
Bo Bae Lee, Ji Hyun Kim, TaeSoo Kim
RNA polymerase II-interacting the Set2 methyltransferase co-transcriptionally methylates histone H3 at lysine 36 within the body of genes. This modification facilitates histone deacetylation by Rpd3S HDAC in 3' transcribed regions to suppress cryptic initiation and slow elongation. Although this pathway is important for global deacetylation, no strong effects on genome-wide transcription have been seen under optimized laboratory conditions. In contrast, this pathway slows the kinetics of mRNA induction when target genes are induced upon environmental changes...
March 21, 2017: BMB Reports
https://www.readbyqxmd.com/read/28318822/genome-wide-analysis-of-rna-polymerase-ii-termination-at-protein-coding-genes
#9
Carlo Baejen, Jessica Andreani, Phillipp Torkler, Sofia Battaglia, Bjoern Schwalb, Michael Lidschreiber, Kerstin C Maier, Andrea Boltendahl, Petra Rus, Stephanie Esslinger, Johannes Söding, Patrick Cramer
At the end of protein-coding genes, RNA polymerase (Pol) II undergoes a concerted transition that involves 3'-processing of the pre-mRNA and transcription termination. Here, we present a genome-wide analysis of the 3'-transition in budding yeast. We find that the 3'-transition globally requires the Pol II elongation factor Spt5 and factors involved in the recognition of the polyadenylation (pA) site and in endonucleolytic RNA cleavage. Pol II release from DNA occurs in a narrow termination window downstream of the pA site and requires the "torpedo" exonuclease Rat1 (XRN2 in human)...
March 6, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28317540/endophytic-botryosphaeriaceae-including-five-new-species-associated-with-mangrove-trees-in-south-africa
#10
J Alexander Osorio, Casparus J Crous, Z Wilhelm de Beer, Michael J Wingfield, Jolanda Roux
Little is known regarding the fungi, especially fungal pathogens, associated with mangroves in Africa. This includes fungi in the Botryosphaeriaceae that comprise numerous opportunistic, stress-associated pathogens often associated with trees affected by environmental and anthropogenically generated stresses, such as those affecting mangroves. We investigated the occurrence of endophytic Botryosphaeriaceae along the entire distribution of mangroves in South Africa. Asymptomatic branches were collected from ten localities and six mangrove species...
April 2017: Fungal Biology
https://www.readbyqxmd.com/read/28315051/development-of-antibody-modified-chitosan-nanoparticles-for-the-targeted-delivery-of-sirna-across-the-blood-brain-barrier-as-a-strategy-for-inhibiting-hiv-replication-in-astrocytes
#11
Jijin Gu, Karam Al-Bayati, Emmanuel A Ho
RNA interference (RNAi)-mediated gene silencing offers a novel treatment and prevention strategy for human immunodeficiency virus (HIV) infection. HIV was found to infect and replicate in human brain cells and can cause neuroinfections and neurological deterioration. We designed dual-antibody-modified chitosan/small interfering RNA (siRNA) nanoparticles to deliver siRNA across the blood-brain barrier (BBB) targeting HIV-infected brain astrocytes as a strategy for inhibiting HIV replication. We hypothesized that transferrin antibody and bradykinin B2 antibody could specifically bind to the transferrin receptor (TfR) and bradykinin B2 receptor (B2R), respectively, and deliver siRNA across the BBB into astrocytes as potential targeting ligands...
March 17, 2017: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/28304334/kdm2-family-members-are-regulated-by-hif-1-in-hypoxia
#12
Michael Batie, Jimena Druker, Laura D'Ignazio, Sonia Rocha
Hypoxia is not only a developmental cue but also a stress and pathological stimulus in many human diseases. The response to hypoxia at the cellular level relies on the activity of the transcription factor family, hypoxia inducible factor (HIF). HIF-1 is responsible for the acute response and transactivates a variety of genes involved in cellular metabolism, cell death, and cell growth. Here, we show that hypoxia results in increased mRNA levels for human lysine (K)-specific demethylase 2 (KDM2) family members, KDM2A and KDM2B, and also for Drosophila melanogaster KDM2, a histone and protein demethylase...
March 17, 2017: Cells
https://www.readbyqxmd.com/read/28301878/sequence-specific-thermodynamic-properties-of-nucleic-acids-influence-both-transcriptional-pausing-and-backtracking-in-yeast
#13
Martin Lukačišin, Matthieu Landon, Rishi Jajoo
RNA Polymerase II pauses and backtracks during transcription, with many consequences for gene expression and cellular physiology. Here, we show that the energy required to melt double-stranded nucleic acids in the transcription bubble predicts pausing in Saccharomyces cerevisiae far more accurately than nucleosome roadblocks do. In addition, the same energy difference also determines when the RNA polymerase backtracks instead of continuing to move forward. This data-driven model corroborates-in a genome wide and quantitative manner-previous evidence that sequence-dependent thermodynamic features of nucleic acids influence both transcriptional pausing and backtracking...
2017: PloS One
https://www.readbyqxmd.com/read/28301289/genome-wide-characterization-of-mediator-recruitment-function-and-regulation
#14
Sebastian Grünberg, Gabriel E Zentner
Mediator is a conserved and essential coactivator complex broadly required for RNA polymerase II (RNAPII) transcription. Recent genome-wide studies of Mediator binding in budding yeast have revealed new insights into the functions of this critical complex and raised new questions about its role in the regulation of gene expression.
February 8, 2017: Transcription
https://www.readbyqxmd.com/read/28300169/double-flow-focused-liquid-injector-for-efficient-serial-femtosecond-crystallography
#15
Dominik Oberthuer, Juraj Knoška, Max O Wiedorn, Kenneth R Beyerlein, David A Bushnell, Elena G Kovaleva, Michael Heymann, Lars Gumprecht, Richard A Kirian, Anton Barty, Valerio Mariani, Aleksandra Tolstikova, Luigi Adriano, Salah Awel, Miriam Barthelmess, Katerina Dörner, P Lourdu Xavier, Oleksandr Yefanov, Daniel R James, Garrett Nelson, Dingjie Wang, George Calvey, Yujie Chen, Andrea Schmidt, Michael Szczepek, Stefan Frielingsdorf, Oliver Lenz, Edward Snell, Philip J Robinson, Božidar Šarler, Grega Belšak, Marjan Maček, Fabian Wilde, Andrew Aquila, Sébastien Boutet, Mengning Liang, Mark S Hunter, Patrick Scheerer, John D Lipscomb, Uwe Weierstall, Roger D Kornberg, John C H Spence, Lois Pollack, Henry N Chapman, Saša Bajt
Serial femtosecond crystallography requires reliable and efficient delivery of fresh crystals across the beam of an X-ray free-electron laser over the course of an experiment. We introduce a double-flow focusing nozzle to meet this challenge, with significantly reduced sample consumption, while improving jet stability over previous generations of nozzles. We demonstrate its use to determine the first room-temperature structure of RNA polymerase II at high resolution, revealing new structural details. Moreover, the double flow-focusing nozzles were successfully tested with three other protein samples and the first room temperature structure of an extradiol ring-cleaving dioxygenase was solved by utilizing the improved operation and characteristics of these devices...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28298358/identification-of-%C3%AE-catenin-interacting-proteins-in-nuclear-fractions-of-native-rat-collecting-duct-cells
#16
Jacqueline R Hwang, Chung-Lin Chou, Barbara Medvar, Mark A Knepper, Hyun Jun Jung
The gene encoding the aquaporin-2 water channel is regulated transcriptionally in response to vasopressin. In the renal collecting duct, vasopressin stimulates the nuclear translocation and phosphorylation (at Ser552) of β-catenin, a multifunctional protein that acts as a transcriptional co-regulator in the nucleus. The purpose of this study was to identify β-catenin interacting proteins that may be involved in transcriptional regulation in rat inner medullary collecting duct (IMCD) cells using both experimental and computational approaches...
March 15, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28292928/cockayne-syndrome-b-protein-regulates-recruitment-of-the-elongin-a-ubiquitin-ligase-to-sites-of-dna-damage
#17
Juston C Weems, Brian D Slaughter, Jay R Unruh, Stefan Boeing, Shawn M Hall, Merry B McLaird, Takashi Yasukawa, Teijiro Aso, Jesper Q Svejstrup, Joan W Conaway, Ronald C Conaway
Elongin A performs dual functions as the transcriptionally active subunit of RNA polymerase II (Pol II) elongation factor Elongin and as the substrate recognition subunit of a Cullin-RING E3 ubiquitin ligase that ubiquitylates Pol II in response to DNA damage. Assembly of the Elongin A ubiquitin ligase and its recruitment to sites of DNA damage is a tightly regulated process induced by DNA damaging agents and α-amanitin, a drug that induces Pol II stalling. In this report, we demonstrate (i) that Elongin A and the ubiquitin ligase subunit CUL5 associate in cells with the Cockayne syndrome B (CSB) protein and (ii) that this interaction is also induced by DNA damage agents and α-amanitin...
March 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28292424/btbd18-regulates-a-subset-of-pirna-generating-loci-through-transcription-elongation-in-mice
#18
Liquan Zhou, Bertram Canagarajah, Yangu Zhao, Boris Baibakov, Keizo Tokuhiro, Dragan Maric, Jurrien Dean
PIWI-interacting RNAs (piRNAs) are small non-coding RNAs essential for animal germ cell development. Despite intense investigation of post-transcriptional processing, chromatin regulators for piRNA biogenesis in mammals remain largely unexplored. Here we document that BTBD18 is a pachytene nuclear protein in mouse testes that occupies a subset of pachytene piRNA-producing loci. Ablation of Btbd18 in mice disrupts piRNA biogenesis, prevents spermiogenesis, and results in male sterility. Transcriptome profiling, chromatin accessibility, and RNA polymerase II occupancy demonstrate that BTBD18 facilitates expression of pachytene piRNA precursors by promoting transcription elongation...
March 13, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28291796/the-effect-of-acetaminophen-on-ubiquitin-homeostasis-in-saccharomyces-cerevisiae
#19
Angelina Huseinovic, Jolanda S van Leeuwen, Tibor van Welsem, Iris Stulemeijer, Fred van Leeuwen, Nico P E Vermeulen, Jan M Kooter, J Chris Vos
Acetaminophen (APAP), although considered a safe drug, is one of the major causes of acute liver failure by overdose, and therapeutic chronic use can cause serious health problems. Although the reactive APAP metabolite N-acetyl-p-benzoquinoneimine (NAPQI) is clearly linked to liver toxicity, toxicity of APAP is also found without drug metabolism of APAP to NAPQI. To get more insight into mechanisms of APAP toxicity, a genome-wide screen in Saccharomyces cerevisiae for APAP-resistant deletion strains was performed...
2017: PloS One
https://www.readbyqxmd.com/read/28289142/transcriptional-interference-by-rna-polymerase-iii-affects-expression-of-the-polr3e-gene
#20
Meghdad Yeganeh, Viviane Praz, Pascal Cousin, Nouria Hernandez
Overlapping gene arrangements can potentially contribute to gene expression regulation. A mammalian interspersed repeat (MIR) nested in antisense orientation within the first intron of the Polr3e gene, encoding an RNA polymerase III (Pol III) subunit, is conserved in mammals and highly occupied by Pol III. Using a fluorescence assay, CRISPR/Cas9-mediated deletion of the MIR in mouse embryonic stem cells, and chromatin immunoprecipitation assays, we show that the MIR affects Polr3e expression through transcriptional interference...
February 15, 2017: Genes & Development
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