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RNA Polymerase II

Rui Chen, Wenjia Xia, Xiaoxiao Wang, Mantang Qiu, Rong Yin, Siwei Wang, Xiaoxiang Xi, Jie Wang, Youtao Xu, Gaochao Dong, Lin Xu, Wei De
Esophageal cancer is one of the most common types of malignant tumors located within the digestive system, with >50% of esophageal cancer cases worldwide occurring in China. Recent studies have demonstrated that long non-coding RNAs (lncRNAs) are frequently dysregulated in cancer; however, few lncRNAs have been characterized in esophageal squamous cell carcinoma (ESCC). In the present study, a novel lncRNA, SET-binding factor 2 (SBF2) antisense RNA1 (SBF2-AS1) was exhibited in ESCC. Expression levels of SBF2-AS1 in ESCC and adjacent non-cancerous tissues were detected using the reverse transcription-quantitative polymerase chain reaction...
April 2018: Oncology Letters
Xiangyang Liu, Lucas Farnung, Christoph Wigge, Patrick Cramer
RNA polymerase II (Pol II) is the central enzyme that transcribes eukaryotic protein-coding genes to produce mRNA. The mushroom toxin α-amanitin binds Pol II and inhibits transcription at the step of RNA chain elongation. Pol II from yeast binds α-amanitin with micromolar affinity, whereas metazoan Pol II enzymes exhibit nanomolar affinities. Here, we present the high-resolution cryo-EM structure of α-amanitin bound to and inhibited by its natural target, the mammalian Pol II elongation complex. The structure revealed that the toxin is located in a pocket previously identified in yeast Pol II, but forms additional contacts with metazoan-specific residues, which explain why its affinity to mammalian Pol II is ~3000 times higher than for yeast Pol II...
March 17, 2018: Journal of Biological Chemistry
Te-Sha Tsai, Sonika Tyagi, Justin C St John
STUDY QUESTION: What are the molecular differences between mitochondrial DNA (mtDNA)-deficient and mtDNA-normal oocytes and how does mitochondrial supplementation alter these? SUMMARY ANSWER: Changes to DNA methylation in a 5' cytosine-phosphate-guanine 3' (CpG) island in the mtDNA-specific replication factor (DNA polymerase gamma (POLG)) of mtDNA-deficient oocytes mediates an increase in mtDNA copy number by the 2-cell stage that positively modulates the expression of nuclear genes, which affect cellular and metabolic processes, following autologous mitochondrial supplementation...
March 13, 2018: Human Reproduction
Elizabeth C Curran, Hui Wang, Thomas R Hinds, Ning Zheng, Edith H Wang
The general transcription factor IID (TFIID) is the first component of the preinitiation complex (PIC) to bind the core promoter of RNA polymerase II transcribed genes. Despite its critical role in protein-encoded gene expression, how TFIID engages promoter DNA remains elusive. We have previously revealed a winged-helix DNA-binding domain in the N-terminal region of the largest TFIID subunit, TAF1. Here, we report the identification of a second DNA-binding module in the C-terminal half of human TAF1, which is encoded by a previously uncharacterized conserved zinc knuckle domain...
March 15, 2018: Scientific Reports
Tie Li, Christopher D Cox, Byram Ozer, Nhung T Nguyen, Huytram N Nguyen, Thomas J Lai, Sichen Li, Fei Liu, Harley I Kornblum, Linda M Liau, Phioanh Leia Nghiemphu, Timothy F Cloughesy, Albert Lai
Mutant isocitrate dehydrogenase (IDH) 1/2 converts α-ketoglutarate (α-KG) to D-2 hydroxyglutarate (D-2-HG), a putative oncometabolite that can inhibit α-KG dependent enzymes, including ten-eleven translocation methylcytosine dioxygenase (TET) DNA demethylases. We recently established that miRNAs are components of the IDH1 mutant-associated glioma CpG island methylator phenotype (G-CIMP), and specifically identified MIR148A as a tumor-suppressive miRNA within G-CIMP. However, the precise mechanism by which mutant IDH induces hypermethylation of MIR148A and other G-CIMP promoters remains to be elucidated...
March 15, 2018: Molecular Cancer Research: MCR
Dinghui Yu, Ying Tan, Molee Chakraborty, Seth Tomchik, Ronald L Davis
The evolutionarily conserved Elongator Complex associates with RNA polymerase II for transcriptional elongation. Elp3 is the catalytic subunit, contains histone acetyltransferase activity, and is associated with neurodegeneration in humans. Elp1 is a scaffolding subunit and when mutated causes familial dysautonomia. Here, we show that elp3 and elp1 are required for aversive long-term olfactory memory in Drosophila RNAi knockdown of elp3 in adult mushroom bodies impairs long-term memory (LTM) without affecting earlier forms of memory...
April 2018: Learning & Memory
Hetal Patel, Manikandan Periyasamy, Georgina P Sava, Alexander Bondke, Brian W Slafer, Sebastian H B Kroll, Marion Barbazanges, Richard Starkey, Silvia Ottaviani, Alison Harrod, Eric O Aboagye, Laki Buluwela, Matthew J Fuchter, Anthony G M Barrett, Charles Coombes, Simak Ali
Recent reports indicate that some cancer types are especially sensitive to transcription inhibition, suggesting that targeting the transcriptional machinery provides new approaches to cancer treatment. Cyclin-dependent kinase (CDK)7 is necessary for transcription, and acts by phosphorylating the C-terminal domain (CTD) of RNA polymerase II (PolII) to enable transcription initiation. CDK7 additionally regulates the activities of a number of transcription factors, including Estrogen receptor-α (ER). Here we describe a new, orally bioavailable CDK7 inhibitor, ICEC0942...
March 15, 2018: Molecular Cancer Therapeutics
Jing Chen, Yan Qi, Cui-Fang Liu, Jing-Min Lu, Yan Shi
INTRODUCTION: MicroRNAs have been increasing prevalent due to the association of their deregulation with neurodegenerative disorders, especially Alzheimer's disease (AD). However, the association between miRNAs and AD hasn't been made clear. PURPOSE: In this study, Nine representative miRNA datasets were selected for the identification of the critical miRNAs by analyzing the overlap relations among them. TargetScan software was further used to predict the target genes of these miRNAs...
March 15, 2018: Journal of Gene Medicine
Tingchao Mao, Chengquan Han, Ruizhi Deng, Biao Wei, Peng Meng, Yan Luo, Yong Zhang
Epigenetic modifications extensively occur in mammalian embryonic development and cell differentiation process. They play an essential role in the reprogramming of nuclei during somatic cell nuclear transfer (SCNT) and subsequent in vitro embryonic development. Recently, SCNT embryos have been verified to contain a subnormal level of histone H3K4 dimethylation (H3K4me2) in contrast to in vitro fertilized embryos. This finding suggested that increasing H3K4me2 levels may ameliorate the aberrant development of cloned embryos...
March 15, 2018: Systems Biology in Reproductive Medicine
Lina Rustanti, Hongping Jin, Dongsheng Li, Mary Lor, Haran Sivakumaran, David Harrich
Nullbasic is a mutant form of HIV-1 Tat that has strong ability to protect cells from HIV-1 replication by inhibiting three different steps of viral replication: reverse transcription, Rev export of viral mRNA from the nucleus to the cytoplasm and transcription of viral mRNA by RNA polymerase II. We previously showed that Nullbasic inhibits transduction of human cells including T cells by HIV-1-based lentiviral vectors. Here we investigated whether the Nullbasic antagonists huTat2 (a Tat targeting intrabody), HIV-1 Tat or Rev proteins or cellular DDX1 protein could improve transduction by a HIV-1 lentiviral vector conveying Nullbasic-ZsGreen1 to human T cells...
March 14, 2018: Virologica Sinica
Neftali Vazquez, Lilia Sanchez, Rebecca Marks, Eduardo Martinez, Victor Fanniel, Alma Lopez, Andrea Salinas, Itzel Flores, Jesse Hirschmann, Robert Gilkerson, Erin Schuenzel, Robert Dearth, Reginald Halaby, Wendy Innis-Whitehouse, Megan Keniry
BACKGROUND: Clustered regularly interspaced short palindromic repeat (CRISPR) RNA-guided adaptive immune systems are found in prokaryotes to defend cells from foreign DNA. CRISPR Cas9 systems have been modified and employed as genome editing tools in wide ranging organisms. Here, we provide a detailed protocol to truncate genes in mammalian cells using CRISPR Cas9 editing. We describe custom donor vector construction using Gibson assembly with the commonly utilized pcDNA3 vector as the backbone...
March 14, 2018: BMC Molecular Biology
Abdullah M S Al-Hatmi, Sarah A Ahmed, Anne D van Diepeningen, Miranda Drogari-Apiranthitou, Paul E Verweij, Jacques F Meis, G Sybren de Hoog
The Fusarium solani species complex (FSSC) is the most common group of fusaria associated with superficial and life-threatening infections in humans. Here we formally introduce Fusarium metavorans sp. nov., widely known as FSSC6 (Fusarium solani species complex lineage 6), one of the most frequent agents of human opportunistic infections. The species is described with multilocus molecular data including sequences of internal transcribed spacer region (ITS), portions of the translation elongation factor 1-a gene (TEF1), and the partial RNA polymerase II gene (rPB2)...
April 1, 2018: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
Teresa Iturriaga, Katherine F LoBuglio, Donald H Pfister
Bulgariella pulla (Leotiomycetes) is redescribed with the addition of characters of the ascus, spores, and habitat that were previously unconsidered. The ascus dehiscence mechanism in Bulgariella is unusual among Leotiomycetes. In this genus, asci lack a pore and open by splitting to form valves. Phylogenetic analyses of partial sequences of translation elongation factor 1-α (TEF1-α), the second largest subunit of RNA polymerase II (RPB2), and the 18S and 28S nuc rRNA genes determined that Bulgariella belongs within Leotiomycetes but without conclusive assignment to an order or family...
March 9, 2018: Mycologia
Ossama A Ahmed, Hany H Kaisar, Rehab Badawi, Nehad Hawash, Hossam Samir, Sherif St Shabana, Mohamed Hassan A Fouad, Fatma H Rizk, Samy A Khodeir, Sherief Abd-Elsalam
Background and aims: Treatment of hepatitis C virus (HCV) infection has significantly changed during the last few years. The combination of ledipasvir and sofosbuvir has been shown to treat high proportions of patients with HCV genotype 1 with remarkable tolerability. The aim of the work was to assess the efficacy and safety of sofosbuvir plus ledipasvir in treating treatment-naïve Egyptian patients with genotype 4 HCV infection. Patients and methods: In this open-label randomized study, 200 treatment-naive patients who were HCV antibody positive and HCV RNA positive by polymerase chain reaction, aged >18 years, were enrolled...
2018: Infection and Drug Resistance
Changliang Peng, Yan Song, Wei Chen, Xiaoying Wang, Xiaoli Liu, Fang Wang, Dongjin Wu, Shengzhong Ma, Xiuwen Wang, Chunzheng Gao
Feline leukemia virus subgroup C receptor 1 (FLVCR1) has been reported to have a crucial role in variety of biological processes, including cell proliferation, cell death, apoptosis, oxidative stress response, cellular differentiation and metabolism. However, little is known about its role in synovial sarcoma (SS). In the current study, FLVCR1 expression was analyzed in two SS cell lines (SW982 and HS-SY-II), and in eight SS tissues and paired adjacent non-tumor tissues using reverse transcription-quantitative polymerase chain reaction, western blot analysis and immunohistochemistry...
March 8, 2018: International Journal of Oncology
Alex Pines, Madelon Dijk, Matthew Makowski, Elisabeth M Meulenbroek, Mischa G Vrouwe, Yana van der Weegen, Marijke Baltissen, Pim J French, Martin E van Royen, Martijn S Luijsterburg, Leon H Mullenders, Michiel Vermeulen, Wim Vermeulen, Navraj S Pannu, Haico van Attikum
Transcription-blocking DNA lesions are removed by transcription-coupled nucleotide excision repair (TC-NER) to preserve cell viability. TC-NER is triggered by the stalling of RNA polymerase II at DNA lesions, leading to the recruitment of TC-NER-specific factors such as the CSA-DDB1-CUL4A-RBX1 cullin-RING ubiquitin ligase complex (CRLCSA ). Despite its vital role in TC-NER, little is known about the regulation of the CRLCSA complex during TC-NER. Using conventional and cross-linking immunoprecipitations coupled to mass spectrometry, we uncover a stable interaction between CSA and the TRiC chaperonin...
March 12, 2018: Nature Communications
Marcelo Bueno Batista, Govind Chandra, Rose Adele Monteiro, Emanuel Maltempi de Souza, Ray Dixon
Bacteria adjust the composition of their electron transport chain (ETC) to efficiently adapt to oxygen gradients. This involves differential expression of various ETC components to optimize energy generation. In Herbaspirillum seropedicae, reprogramming of gene expression in response to oxygen availability is controlled at the transcriptional level by three Fnr orthologs. Here, we characterised Fnr regulons using a combination of RNA-Seq and ChIP-Seq analysis. We found that Fnr1 and Fnr3 directly regulate discrete groups of promoters (Groups I and II, respectively), and that a third group (Group III) is co-regulated by both transcription factors...
February 26, 2018: Nucleic Acids Research
Marina E Borisova, Andrea Voigt, Maxim A X Tollenaere, Sanjeeb Kumar Sahu, Thomas Juretschke, Nastasja Kreim, Niels Mailand, Chunaram Choudhary, Simon Bekker-Jensen, Masato Akutsu, Sebastian A Wagner, Petra Beli
Ultraviolet (UV) light radiation induces the formation of bulky photoproducts in the DNA that globally affect transcription and splicing. However, the signaling pathways and mechanisms that link UV-light-induced DNA damage to changes in RNA metabolism remain poorly understood. Here we employ quantitative phosphoproteomics and protein kinase inhibition to provide a systems view on protein phosphorylation patterns induced by UV light and uncover the dependencies of phosphorylation events on the canonical DNA damage signaling by ATM/ATR and the p38 MAP kinase pathway...
March 9, 2018: Nature Communications
Michael Babokhov, Mohammad M Mosaheb, Richard W Baker, Stephen M Fuchs
The C-terminal domain (CTD) of the largest subunit of RNA polymerase II (RNAPII) is required to regulate transcription and to integrate it with other essential cellular processes. In the budding yeast Saccharomyces cerevisiae , the CTD of Rpb1p consists of 26 conserved heptad repeats that are post-translationally modified to orchestrate protein factor binding at different stages of the transcription cycle. A long-standing question in the study of the CTD is if there are any functional differences between the 26 repeats...
March 9, 2018: G3: Genes—Genomes—Genetics
Hyemin Yoon, Hoon Jang, Eun-Young Kim, Sohyeon Moon, Sangho Lee, Minha Cho, Hye Jung Cho, Jung Jae Ko, Eun Mi Chang, Kyung-Ah Lee, Youngsok Choi
BACKGROUND/AIMS: Cyclic adenosine monophosphate (cAMP)-dependent type 2 regulatory subunit beta (Prkar2b) is a regulatory isoform of cAMP-dependent protein kinase (PKA), which is the primary target for cAMP actions. In oocytes, PKA and the pentose phosphate pathway (PPP) have important roles during the germinal vesicle (GV) stage arrest of development. Although the roles of the PKA signal pathway have been studied in the development of oocyte, there has been no report on the function of PRKAR2B, a key regulator of PKA...
March 2, 2018: Cellular Physiology and Biochemistry
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