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https://www.readbyqxmd.com/read/28538188/identification-and-characterization-of-a-class-of-malat1-like-genomic-loci
#1
Bin Zhang, Yuntao S Mao, Sarah D Diermeier, Irina V Novikova, Eric P Nawrocki, Tom A Jones, Zsolt Lazar, Chang-Shung Tung, Weijun Luo, Sean R Eddy, Karissa Y Sanbonmatsu, David L Spector
The MALAT1 (Metastasis-Associated Lung Adenocarcinoma Transcript 1) gene encodes a noncoding RNA that is processed into a long nuclear retained transcript (MALAT1) and a small cytoplasmic tRNA-like transcript (mascRNA). Using an RNA sequence- and structure-based covariance model, we identified more than 130 genomic loci in vertebrate genomes containing the MALAT1 3' end triple-helix structure and its immediate downstream tRNA-like structure, including 44 in the green lizard Anolis carolinensis. Structural and computational analyses revealed a co-occurrence of components of the 3' end module...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28535337/overall-structural-model-of-ns5a-protein-from-hepatitis-c-virus-and-modulation-by-mutations-confering-resistance-of-virus-replication-to-cyclosporin-a
#2
Aurelie Badillo, Veronique Brechot, Stephane Sarrazin, François-Xavier Cantrelle, Frederic Delolme, Marie-Laure Fogeron, Jennifer Molle, Roland Montserret, Anja Bockmann, Ralf Bartenschlager, Volker Lohmann, Guy Lippens, Sylvie Ricard-Blum, Xavier Hanoulle, Francois Penin
Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is a RNA-binding phosphoprotein composed of a N-terminal membrane anchor (AH), a structured domain 1 (D1) and two intrinsically disordered domains (D2 and D3). The knowledge of the functional architecture of this multifunctional protein remains limited. We report here that NS5A-D1D2D3 produced in a wheat germ cell-free system is obtained under a highly phosphorylated state. Its NMR analysis revealed that these phosphorylations do not change the disordered nature of D2 and D3 domains but increase the number of conformers due to partial phosphorylations...
May 23, 2017: Biochemistry
https://www.readbyqxmd.com/read/28534981/loss-of-csmd1-expression-disrupts-mammary-duct-formation-while-enhancing-proliferation-migration-and-invasion
#3
Mohamed Kamal, Deborah L Holliday, Ewan E Morrison, Valerie Speirs, Carmel Toomes, Sandra M Bell
The CUB and sushi multiple domains 1 (CSMD1) gene maps to chromosome 8p23, a region deleted in many cancers. Loss of CSMD1 expression is associated with poor prognosis in breast cancer suggesting that it acts as a tumour suppressor in this cancer. However, the function of CSMD1 is largely unknown. Herein, we investigated CSMD1 functions in cell line models. CSMD1 expression was suppressed in MCF10A and LNCaP cells using short hairpin RNA. Functional assays were performed focusing on the 'normal' MCF10A cell line...
May 22, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28533023/the-rna-modification-n-6-methyladenosine-and-its-implications-in-human-disease
#4
REVIEW
Pedro J Batista
Impaired gene regulation lies at the heart of many disorders, including developmental diseases and cancer. Furthermore, the molecular pathways that control gene expression are often the target of cellular parasites, such as viruses. Gene expression is controlled through multiple mechanisms that are coordinated to ensure the proper and timely expression of each gene. Many of these mechanisms target the life cycle of the RNA molecule, from transcription to translation. Recently, another layer of regulation at the RNA level involving RNA modifications has gained renewed interest of the scientific community...
May 19, 2017: Genomics, Proteomics & Bioinformatics
https://www.readbyqxmd.com/read/28532394/circularlogo-a-lightweight-web-application-to-visualize-intra-motif-dependencies
#5
Zhenqing Ye, Tao Ma, Michael T Kalmbach, Surendra Dasari, Jean-Pierre A Kocher, Liguo Wang
BACKGROUND: The sequence logo has been widely used to represent DNA or RNA motifs for more than three decades. Despite its intelligibility and intuitiveness, the traditional sequence logo is unable to display the intra-motif dependencies and therefore is insufficient to fully characterize nucleotide motifs. Many methods have been developed to quantify the intra-motif dependencies, but fewer tools are available for visualization. RESULT: We developed CircularLogo, a web-based interactive application, which is able to not only visualize the position-specific nucleotide consensus and diversity but also display the intra-motif dependencies...
May 22, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28532216/structural-insights-into-the-eukaryotic-transcription-initiation-machinery
#6
Eva Nogales, Robert K Louder, Yuan He
Eukaryotic gene transcription requires the assembly at the promoter of a large preinitiation complex (PIC) that includes RNA polymerase II (Pol II) and the general transcription factors TFIID, TFIIA, TFIIB, TFIIF, TFIIE, and TFIIH. The size and complexity of Pol II, TFIID, and TFIIH have precluded their reconstitution from heterologous systems, and purification relies on scarce endogenous sources. Together with their conformational flexibility and the transient nature of their interactions, these limitations had precluded structural characterization of the PIC...
May 22, 2017: Annual Review of Biophysics
https://www.readbyqxmd.com/read/28531330/structural-basis-for-substrate-binding-and-catalytic-mechanism-of-a-human-rna-m5c-methyltransferase-nsun6
#7
Ru-Juan Liu, Tao Long, Jing Li, Hao Li, En-Duo Wang
5-methylcytosine (m5C) modifications of RNA are ubiquitous in nature and play important roles in many biological processes such as protein translational regulation, RNA processing and stress response. Aberrant expressions of RNA:m5C methyltransferases are closely associated with various human diseases including cancers. However, no structural information for RNA-bound RNA:m5C methyltransferase was available until now, hindering elucidation of the catalytic mechanism behind RNA:m5C methylation. Here, we have solved the structures of NSun6, a human tRNA:m5C methyltransferase, in the apo form and in complex with a full-length tRNA substrate...
May 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28531277/genome-wide-discovery-of-viral-micrornas-based-on-phylogenetic-analysis-and-structural-evolution-of-various-human-papillomavirus-subtypes
#8
Shun-Long Weng, Kai-Yao Huang, Julia Tzu-Ya Weng, Fang-Yu Hung, Tzu-Hao Chang, Tzong-Yi Lee
In mammals, microRNAs (miRNAs) play key roles in controlling posttranscriptional regulation through binding to the mRNAs of target genes. Recently, it was discovered that viral miRNAs may be involved in human cancers and diseases. It is likely that viral miRNAs help viruses enter the latent phase of their life cycle and become undetected by the host's immune system, while increasing the host's risk for cancer development. Cervical cancer is typically related to the infection of human papillomavirus (HPV) through sexual transmission...
May 20, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/28531189/tandem-duplications-lead-to-novel-expression-patterns-through-exon-shuffling-in-drosophila-yakuba
#9
Rebekah L Rogers, Ling Shao, Kevin R Thornton
One common hypothesis to explain the impacts of tandem duplications is that whole gene duplications commonly produce additive changes in gene expression due to copy number changes. Here, we use genome wide RNA-seq data from a population sample of Drosophila yakuba to test this 'gene dosage' hypothesis. We observe little evidence of expression changes in response to whole transcript duplication capturing 5' and 3' UTRs. Among whole gene duplications, we observe evidence that dosage sharing across copies is likely to be common...
May 22, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28531167/a-role-for-the-host-dna-damage-response-in-hepatitis-b-virus-cccdna-formation-and-beyond
#10
REVIEW
Sabrina Schreiner, Michael Nassal
Chronic hepatitis B virus (HBV) infection puts more than 250 million people at a greatly increased risk to develop end-stage liver disease. Like all hepadnaviruses, HBV replicates via protein-primed reverse transcription of a pregenomic (pg) RNA, yielding an unusually structured, viral polymerase-linked relaxed-circular (RC) DNA as genome in infectious particles. Upon infection, RC-DNA is converted into nuclear covalently closed circular (ccc) DNA. Associating with cellular proteins into an episomal minichromosome, cccDNA acts as template for new viral RNAs, ensuring formation of progeny virions...
May 22, 2017: Viruses
https://www.readbyqxmd.com/read/28530833/discovery-of-small-molecules-for-repressing-cap-independent-translation-of-human-vascular-endothelial-growth-factor-hvegf-as-novel-anti-tumor-agents
#11
Shi-Ke Wang, Yue Wu, Xiao-Qin Wang, Guo-Tao Kuang, Qi Zhang, Shu-Ling Lin, Hui-Yun Liu, Jia-Heng Tan, Zhi-Shu Huang, Tian-Miao Ou
Angiogenesis is important in tumorigenesis and tumor progression. Human vascular endothelial growth factor (hVEGF) is an angiogenic growth factor that plays a crucial role in tumor progression. The G-rich region within the 5'-untranslated region (5'-UTR) of hVEGF mRNA can form a 'switchable' RNA G-quadruplex structure that is essential for a cap-independent translation initiation. We screened our small-molecule library for binders of this G-tract. One novel quinazoline derivative, compound 1, showed a significant specific interaction with the G-tract and destabilized the G-quadruplex structure...
May 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28530607/metabolic-and-rna-profiling-elucidates-proanthocyanidins-accumulation-in-aglianico-grape
#12
Alessandra Rinaldi, Clizia Villano, Carmine Lanzillo, Angelo Tamburrino, Michael Jourdes, Pierre-Louis Teissedre, Luigi Moio, Luigi Frusciante, Domenico Carputo, Riccardo Aversano
Aglianico grapes are known for their high content of proanthocyanidins (PAs), which are responsible for the astringency of wines derived from this cultivar. However, the accumulation of PAs and their genetic control during berry development remain largely unexplored. This work aimed to monitor astringency-causing PAs in Aglianico berries and correlate them with the expression of 14 key genes. Berries were collected during ripening and dissected in skins and seeds. PAs were fractionated and the content of total phenolics, flavans, anthocyanins, tannins reactive towards salivary proteins and tannin structural composition were evaluated...
October 15, 2017: Food Chemistry
https://www.readbyqxmd.com/read/28530384/divalent-metal-ion-activation-of-a-guanine-general-base-in-the-hammerhead-ribozyme-insights-from-molecular-simulations
#13
Haoyuan Chen, Timothy J Giese, Barbara L Golden, Darrin M York
The hammerhead ribozyme is a well-studied nucleolytic ribozyme that catalyzes the self-cleavage of the RNA phosphodiester backbone. Despite experimental and theoretical efforts, there remain key questions about details of the mechanism with regard to the activation of the nucleophile by the putative general base guanine (G12). Straight-forward interpretation of the measured activity-pH data implies the pKa value of the N1 position in the G12 nucleobase is significantly shifted by the ribozyme environment. Recent crystallographic and biochemical work has identified pH-dependent divalent metal ion binding at the N7/O6 position of G12, leading to the hypothesis that this binding mode could induce a pKa shift of G12 towards neutrality...
May 22, 2017: Biochemistry
https://www.readbyqxmd.com/read/28530165/basic-amino-acids-in-the-n-terminal-half-of-the-pb2-subunit-of-influenza-virus-rna-polymerase-are-involved-in-both-transcription-and-replication
#14
Koyu Hara, Takahito Kashiwagi, Nobuyuki Hamada, Hiroshi Watanabe
The PB2 subunit of influenza virus RNA polymerase is known to be involved in the initiation of transcription of the virus genome via cap binding. However, other specific roles of PB2 for viral RNA synthesis are not well understood. Here, we demonstrate that basic residues, 124R, 142R, 143R, 268R and 331K/332R, in the N-terminal half of PB2 are important for the polymerase activity. Notably, R124A mutation remarkably reduced the synthesis of mRNA, cRNA and vRNA in vivo, which was in good agreement with the data obtained in vitro...
May 22, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28529241/downregulation-of-transcription-factor-sp1-suppresses-malignant-properties-of-a549-human-lung-cancer-cell-line-with-decreased-%C3%AE-4-galactosylation-of-highly-branched-n-glycans
#15
Kodai Muramoto, Riho Tange, Takayuki Ishii, Kana Miyauchi, Takeshi Sato
Dramatic changes in the glycan structures of cell surface proteins have been observed upon malignant transformation of cells as induced by the altered expression levels of glycosyltransferases. Such changes are closely associated with the malignant properties of cancer cells. Transcription factor Sp1 regulates the gene expression of various molecules including glycosyltransferases. Herein, we investigated whether or not Sp1-downregulation affects to N-glycosylation of glycoproteins and malignant properties of A549 human lung carcinoma cell line...
May 20, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28528867/a-pan-cancer-proteogenomic-atlas-of-pi3k-akt-mtor-pathway-alterations
#16
Yiqun Zhang, Patrick Kwok-Shing Ng, Melanie Kucherlapati, Fengju Chen, Yuexin Liu, Yiu Huen Tsang, Guillermo de Velasco, Kang Jin Jeong, Rehan Akbani, Angela Hadjipanayis, Angeliki Pantazi, Christopher A Bristow, Eunjung Lee, Harshad S Mahadeshwar, Jiabin Tang, Jianhua Zhang, Lixing Yang, Sahil Seth, Semin Lee, Xiaojia Ren, Xingzhi Song, Huandong Sun, Jonathan Seidman, Lovelace J Luquette, Ruibin Xi, Lynda Chin, Alexei Protopopov, Thomas F Westbrook, Carl Simon Shelley, Toni K Choueiri, Michael Ittmann, Carter Van Waes, John N Weinstein, Han Liang, Elizabeth P Henske, Andrew K Godwin, Peter J Park, Raju Kucherlapati, Kenneth L Scott, Gordon B Mills, David J Kwiatkowski, Chad J Creighton
Molecular alterations involving the PI3K/AKT/mTOR pathway (including mutation, copy number, protein, or RNA) were examined across 11,219 human cancers representing 32 major types. Within specific mutated genes, frequency, mutation hotspot residues, in silico predictions, and functional assays were all informative in distinguishing the subset of genetic variants more likely to have functional relevance. Multiple oncogenic pathways including PI3K/AKT/mTOR converged on similar sets of downstream transcriptional targets...
May 8, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28528545/discovery-and-biosynthesis-of-gladiolin-a-burkholderia-gladioli-antibiotic-with-promising-activity-against-mycobacterium-tuberculosis
#17
Lijiang Song, Matthew Jenner, Joleen Masschelein, Cerith Jones, Matthew J Bull, Simon R Harris, Ruben C Hartkoorn, Anthony Vocat, Isolda Romero-Canelón, Paul Coupland, Gordon Webster, Matthew Dunn, Rebecca Weiser, Christopher Paisey, Stewart T Cole, Julian Parkhill, Eshwar Mahenthiralingam, Gregory L Challis
An antimicrobial activity screen of Burkholderia gladioli BCC0238, a clinical isolate from a cystic fibrosis patient, led to the discovery of gladiolin, a novel macrolide antibiotic with potent activity against Mycobacterium tuberculosis H37Rv. Gladiolin is structurally-related to etnangien, a highly unstable antibiotic from Sorangium cellulosum that is also active against Mycobacteria. Like etnangien, gladiolin was found to inhibit RNA polymerase, a validated drug target in M. tuberculosis. However, gladiolin lacks the highly labile hexaene moiety of etnangien and was thus found to possess significantly increased chemical stability...
May 22, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28528358/dna-topoisomerase-targeting-chemotherapeutics-what-s-new
#18
REVIEW
Selma M Cuya, Mary-Ann Bjornsti, Robert C A M van Waardenburg
To resolve the topological problems that threaten the function and structural integrity of nuclear and mitochondrial genomes and RNA molecules, human cells encode six different DNA topoisomerases including type IB enzymes (TOP1 and TOP1mt), type IIA enzymes (TOP2α and TOP2β) and type IA enzymes (TOP3α and TOP3β). DNA entanglements and the supercoiling of DNA molecules are regulated by topoisomerases through the introduction of transient enzyme-linked DNA breaks. The covalent topoisomerase-DNA complexes are the cellular targets of a diverse group of cancer chemotherapeutics, which reversibly stabilize these reaction intermediates...
May 20, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28527998/molecular-cloning-and-structural-modelling-of-gamma-phospholipase-a2-inhibitors-from-bothrops-atrox-and-micrurus-lemniscatus-snakes
#19
Carina G Picelli, Rafael J Borges, Carlos A H Fernandes, Fabio M Matioli, Carla F C Fernandes, Juliana C Sobrinho, Rudson J Holanda, Luiz S Ozaki, Anderson M Kayano, Leonardo A Calderon, Marcos R M Fontes, Rodrigo G Stábeli, Andreimar M Soares
Phospholipases A2 inhibitors (PLIs) produced by venomous and non-venomous snakes play essential role in this resistance. These endogenous inhibitors may be classified by their fold in PLIα, PLIβ and PLIγ. Phospholipases A2 (PLA2s) develop myonecrosis in snake envenomation, a consequence that is not efficiently neutralized by antivenom treatment. This work aimed to identify and characterize two PLIs from Amazonian snake species, Bothrops atrox and Micrurus lemniscatus. Liver tissues RNA of specimens from each species were isolated and amplified by RT-PCR using PCR primers based on known PLIγ gene sequences, followed by cloning and sequencing of amplified fragments...
May 17, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28526340/unfolding-the-pathogenesis-of-scleroderma-through-genomics-and-epigenomics
#20
REVIEW
Pei-Suen Tsou, Amr H Sawalha
With unknown etiology, scleroderma (SSc) is a multifaceted disease characterized by immune activation, vascular complications, and excessive fibrosis in internal organs. Genetic studies, including candidate gene association studies, genome-wide association studies, and whole-exome sequencing have supported the notion that while genetic susceptibility to SSc appears to be modest, SSc patients are genetically predisposed to this disease. The strongest genetic association for SSc lies within the MHC region, with loci in HLA-DRB1, HLA-DQB1, HLA-DPB1, and HLA-DOA1 being the most replicated...
May 16, 2017: Journal of Autoimmunity
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