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https://www.readbyqxmd.com/read/29166058/structural-entanglements-in-protein-complexes
#1
Yani Zhao, Mateusz Chwastyk, Marek Cieplak
We consider multi-chain protein native structures and propose a criterion that determines whether two chains in the system are entangled or not. The criterion is based on the behavior observed by pulling at both termini of each chain simultaneously in the two chains. We have identified about 900 entangled systems in the Protein Data Bank and provided a more detailed analysis for several of them. We argue that entanglement enhances the thermodynamic stability of the system but it may have other functions: burying the hydrophobic residues at the interface and increasing the DNA or RNA binding area...
June 14, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/29165680/a-thermus-phage-protein-inhibits-host-rna-polymerase-by-preventing-template-dna-strand-loading-during-open-promoter-complex-formation
#2
Wei-Yang Ooi, Yuko Murayama, Vladimir Mekler, Leonid Minakhin, Konstantin Severinov, Shigeyuki Yokoyama, Shun-Ichi Sekine
RNA polymerase (RNAP) is a major target of gene regulation. Thermus thermophilus bacteriophage P23-45 encodes two RNAP binding proteins, gp39 and gp76, which shut off host gene transcription while allowing orderly transcription of phage genes. We previously reported the structure of the T. thermophilus RNAP•σA holoenzyme complexed with gp39. Here, we solved the structure of the RNAP•σA holoenzyme bound with both gp39 and gp76, which revealed an unprecedented inhibition mechanism by gp76. The acidic protein gp76 binds within the RNAP cleft and occupies the path of the template DNA strand at positions -11 to -4, relative to the transcription start site at +1...
November 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29165589/ns3-helicase-from-dengue-virus-specifically-recognizes-viral-rna-sequence-to-ensure-optimal-replication
#3
Crystall M D Swarbrick, Chandrakala Basavannacharya, Kitti W K Chan, Shu-Ann Chan, Daljit Singh, Na Wei, Wint Wint Phoo, Dahai Luo, Julien Lescar, Subhash G Vasudevan
The protein-RNA interactions within the flavivirus replication complex (RC) are not fully understood. Our structure of dengue virus NS3 adenosine triphosphatase (ATPase)/helicase bound to the conserved 5' genomic RNA 5'-AGUUGUUAGUCU-3' reveals that D290 and R538 make specific interactions with G2 and G5 bases respectively. We show that single-stranded 12-mer RNA stimulates ATPase activity of NS3, however the presence of G2 and G5 leads to significantly higher activation. D290 is adjacent to the DEXH motif found in SF2 helicases like NS3 and interacts with R387, forming a molecular switch that activates the ATPase site upon RNA binding...
November 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29165587/identification-of-diverse-target-rnas-that-are-functionally-regulated-by-human-pumilio-proteins
#4
Jennifer A Bohn, Jamie L Van Etten, Trista L Schagat, Brittany M Bowman, Richard C McEachin, Peter L Freddolino, Aaron C Goldstrohm
Human Pumilio proteins, PUM1 and PUM2, are sequence specific RNA-binding proteins that regulate protein expression. We used RNA-seq, rigorous statistical testing and an experimentally derived fold change cut-off to identify nearly 1000 target RNAs-including mRNAs and non-coding RNAs-that are functionally regulated by PUMs. Bioinformatic analysis defined a PUM Response Element (PRE) that was significantly enriched in transcripts that increased in abundance and matches the PUM RNA-binding consensus. We created a computational model that incorporates PRE position and frequency within an RNA relative to the magnitude of regulation...
November 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29165116/circular-rna-profiles-in-mouse-lung-tissue-induced-by-radon
#5
Weiwei Pei, Lijing Tao, Leshuai W Zhang, Shuyu Zhang, Jianping Cao, Yang Jiao, Jian Tong, Jihua Nie
BACKGROUND: Radon is a known human lung carcinogen, whose underlying carcinogenic mechanism remains unclear. Recently, circular RNA (circRNA), a class of endogenous non-protein coding RNAs that contain a circular loop, was found to exhibit multiple biological effects. In this study, circRNA profiles in mouse lung tissues between control and radon exposure were analyzed. METHODS: Six mice were exposed to radon at concentration of 100,000 Bq/m(3), 12 h/d, for up to cumulative doses of 60 working level months (WLM)...
April 7, 2017: Environmental Health and Preventive Medicine
https://www.readbyqxmd.com/read/29164876/live-cell-imaging-of-endogenous-rnas-using-pumilio-homology-domain-mutants-principles-and-applications
#6
Hideaki Yoshimura
Recently, dynamic changes in RNA location in space and time in living cells have become a target of interest in biology because of their essential roles in controlling physiological phenomena. To visualize RNA, methods for the fluorescence labeling of RNA in living cells have been developed. For RNA labeling, oligonucleotide-based RNA probes have mainly been used because of their high selectivity for target RNAs. By contrast, protein-based RNA probes have not been used widely because of their lack of design flexibility, although they have various potential advantages compared with nucleotide-based probes, such as controllability of intracellular localization, high detectability, and ease of introduction to cells and transgenic organisms in cell type and tissue specific manner by genetic engineering techniques...
November 22, 2017: Biochemistry
https://www.readbyqxmd.com/read/29164104/targeting-dengue-virus-ns-3-helicase-by-ligand-based-pharmacophore-modeling-and-structure-based-virtual-screening
#7
Sobia A Halim, Shanza Khan, Ajmal Khan, Abdul Wadood, Fazal Mabood, Javid Hussain, Ahmed Al-Harrasi
Dengue fever is an emerging public health concern, with several million viral infections occur annually, for which no effective therapy currently exist. Non-structural protein 3 (NS-3) Helicase encoded by the dengue virus (DENV) is considered as a potential drug target to design new and effective drugs against dengue. Helicase is involved in unwinding of dengue RNA. This study was conducted to design new NS-3 Helicase inhibitor by in silico ligand- and structure based approaches. Initially ligand-based pharmacophore model was generated that was used to screen a set of 1201474 compounds collected from ZINC Database...
2017: Frontiers in Chemistry
https://www.readbyqxmd.com/read/29163372/hyperglycemia-promotes-tmprss2-erg-gene-fusion-in-prostate-cancer-cells-via-upregulating-insulin-like-growth-factor-binding-protein-2
#8
Jeff M P Holly, Jessica Broadhurst, Rehanna Mansor, Amit Bahl, Claire M Perks
Background: Epidemiologic evidence shows that obesity is associated with a greater risk of aggressive prostate cancer (PCa) and PCa-specific mortality and this is observed mainly in men with the TMPRSS2-ERG gene fusion. Obesity is often associated with comorbid conditions such as type 2 diabetes and hyperglycemia: we investigated whether some of the exposures associated with disturbed metabolism can also affect the frequency of this gene fusion. Methods: Fusion was induced in LNCaP PCa cells in normal or high levels of glucose, with or without insulin-like growth factor binding protein-2 (IGFBP-2) silenced or the presence of insulin-like growth factor-1 (IGF-I), insulin, or epidermal growth factor (EGF)...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29163124/the-search-for-an-effective-therapy-to-treat-fragile-x-syndrome-dream-or-reality
#9
REVIEW
Sara Castagnola, Barbara Bardoni, Thomas Maurin
Fragile X Syndrome (FXS) is the most common form of intellectual disability and a primary cause of autism. It originates from the lack of the Fragile X Mental Retardation Protein (FMRP), which is an RNA-binding protein encoded by the Fragile X Mental Retardation Gene 1 (FMR1) gene. Multiple roles have been attributed to this protein, ranging from RNA transport (from the nucleus to the cytoplasm, but also along neurites) to translational control of mRNAs. Over the last 20 years many studies have found a large number of FMRP mRNA targets, but it is still not clear which are those playing a critical role in the etiology of FXS...
2017: Frontiers in Synaptic Neuroscience
https://www.readbyqxmd.com/read/29162978/exploring-the-interaction-of-drosophila-tdp-43-and-the-type-ii-voltage-gated-calcium-channel-cacophony-in-regulating-motor-function-and-behavior
#10
Kayly M Lembke, David B Morton
Amyotrophic lateral sclerosis (ALS) is the most common adult onset motor neurodegenerative disease. The cause of the disease remains obscure, and as such there is no effective treatment or cure. Amyotrophic lateral sclerosis and other neurodegenerative diseases are frequently characterized by dysfunction of the RNA-binding protein, TDP-43. Using model systems to understand the mechanisms underlying TDP-43 dysfunction should accelerate identification of therapeutic targets. A recent report has shown that motor defects caused by the deletion of the Drosophila TDP-43 ortholog, tbph, are not driven by changes in the physiology at the neuromuscular junction...
2017: Journal of Experimental Neuroscience
https://www.readbyqxmd.com/read/29161847/formulation-of-the-protein-synthesis-rate-with-sequence-information
#11
Wenjun Xia, Jinzhi Lei
Translation is a central biological process by which proteins are synthesized from genetic information contained within mRNAs. Here, we investigate the kinetics of translation at the molecular level by a stochastic simulation model. The model explicitly includes RNA sequences, ribosome dynamics, the tRNA pool and biochemical reactions involved in the translation elongation. The results show that the translation efficiency is mainly limited by the available ribosome number, translation initiation and the translation elongation time...
April 1, 2018: Mathematical Biosciences and Engineering: MBE
https://www.readbyqxmd.com/read/29161365/genome-scale-analysis-ofescherichia-coliwith-a-comprehensive-prokaryotic-sequence-based-biophysical-model-of-translation-initiation-and-elongation
#12
Gilad Shaham, Tamir Tuller
Translation initiation in prokaryotes is affected by the mRNA folding and interaction of the ribosome binding site with the ribosomal RNA. The elongation rate is affected, among other factors, by the local biophysical properties of the coding regions, the decoding rates of different codons, and the interactions among ribosomes. Currently, there is no comprehensive biophysical model of translation that enables the prediction of mRNA translation dynamics based only on the transcript sequence and while considering all of these fundamental aspects of translation...
November 17, 2017: DNA Research: An International Journal for Rapid Publication of Reports on Genes and Genomes
https://www.readbyqxmd.com/read/29159897/identification-and-characterization-of-two-variants-of-the-hfq-srna-chaperone-in-the-fish-pathogen-piscirickettsia-salmonis
#13
S H Marshall, P Flores-Herrera, F A Henríquez, F A Gómez
Small RNA and chaperone proteins form synergistic duos that play pivotal roles in controlling gene expression in bacteria. This is the case for Hfq, a highly pleiotropic pretranslational modulator of general protein expression, which responds to harsh environmental conditions and influences fitness and virulence in a wide range of pathogenic Enterobacteria. Given this relevancy, we evaluated the presence and potential role of Hfq in the fish pathogen Piscirickettsia salmonis, a Gram-negative bacterium that threatens the sustainability of Chilean salmon production...
November 21, 2017: Journal of Fish Diseases
https://www.readbyqxmd.com/read/29159556/effects-of-arsenic-trioxide-on-inf-gamma-gene-expression-in-mrl-lpr-mice-and-human-lupus
#14
Hongye Hu, Enjiu Chen, Yongji Li, Xiaochun Zhu, Ting Zhang, Xiaofang Zhu
Arsenic trioxide (As2O3; ATO), a traditional Chinese medicine, is used to treat patients with acute promye-locytic leukemia, while its application for treatment of systemic lupus erythematosus (SLE) is still under evaluation. The high expression of INF-gamma (INF-γ) is a primary pathogenic factor in SLE. It is found that ATO can reduce INF-γ expression levels in lupus-prone mice, whereas it is not clear whether ATO has the same effect on SLE patients. Therefore, this study was to investigate the underlying mechanism of the effects of ATO on the expression of INF-γ in splenocytes of MRL/lpr mice and PBMCs of human lupus...
November 20, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/29158818/identifying-and-characterizing-circrna-protein-interaction
#15
REVIEW
William W Du, Chao Zhang, Weining Yang, Tianqiao Yong, Faryal Mehwish Awan, Burton B Yang
Circular RNAs have been identified as naturally occurring RNAs that are highly represented in the eukaryotic transcriptome. Although a large number of circRNAs have been reported, circRNA functions remain largely unknown. CircRNAs can function as miRNA sponges, thereby reducing their ability to target mRNAs. We hypothesize that circRNAs may bind, store, sort, and sequester proteins to particular subcellular locations, and act as dynamic scaffolding molecules that modulate protein-protein interactions. Here, we review the biological implication and function of circRNA-protein interaction, and reveal a dynamic model of the interaction in various tissues, development stages and physiological conditions...
2017: Theranostics
https://www.readbyqxmd.com/read/29158545/a-potent-cas9-derived-gene-activator-for-plant-and-mammalian-cells
#16
Zhenxiang Li, Dandan Zhang, Xiangyu Xiong, Bingyu Yan, Wei Xie, Jen Sheen, Jian-Feng Li
Overexpression of complementary DNA represents the most commonly used gain-of-function approach for interrogating gene functions and for manipulating biological traits. However, this approach is challenging and inefficient for multigene expression due to increased labour for cloning, limited vector capacity, requirement of multiple promoters and terminators, and variable transgene expression levels. Synthetic transcriptional activators provide a promising alternative strategy for gene activation by tethering an autonomous transcription activation domain (TAD) to an intended gene promoter at the endogenous genomic locus through a programmable DNA-binding module...
November 20, 2017: Nature Plants
https://www.readbyqxmd.com/read/29158441/shep-regulates-drosophila-neuronal-remodeling-by-controlling-transcription-of-its-chromatin-targets
#17
Dahong Chen, Ryan K Dale, Elissa P Lei
Neuronal remodeling is critical to form the mature nervous system and can lead to neuropsychiatric diseases when disrupted. Global gene expression changes in neurons during remodeling as well as the factors that regulate these changes remain poorly defined. To elucidate this process, we performed RNA-seq on isolated Drosophila larval and pupal neurons and found up-regulated synaptic signaling and down-regulated gene expression regulators as a result of normal neuronal metamorphosis. We further tested the role of alan shepard (shep), which encodes an evolutionarily conserved RNA-binding protein required for proper neuronal remodeling...
November 20, 2017: Development
https://www.readbyqxmd.com/read/29158440/cohesin-facilitates-zygotic-genome-activation-in-zebrafish
#18
Michael Meier, Jenny Grant, Amy Dowdle, Amarni Thomas, Jennifer Gerton, Philippe Collas, Justin M O'Sullivan, Julia A Horsfield
At zygotic genome activation (ZGA), changes in chromatin structure are associated with new transcription immediately following the maternal-to-zygotic transition (MZT). The nuclear architectural proteins, cohesin and CCCTC-binding factor (CTCF), contribute to chromatin structure and gene regulation. We show here that normal cohesin function is important for ZGA in zebrafish. Depletion of cohesin subunit Rad21 delays ZGA without affecting cell cycle progression. In contrast, CTCF depletion has little effect on ZGA whereas complete abrogation is lethal...
November 20, 2017: Development
https://www.readbyqxmd.com/read/29158339/genome-wide-mapping-of-decay-factor-mrna-interactions-in-yeast-identifies-nutrient-responsive-transcripts-as-targets-of-the-deadenylase-ccr4
#19
Jason E Miller, Liye Zhang, Haoyang Jiang, Yunfei Li, B Franklin Pugh, Joseph C Reese
The Ccr4-Not complex is a major regulator of stress responses that controls gene expression at multiple levels, from transcription to mRNA decay. Ccr4, a core subunit of the complex, is the main cytoplasmic deadenylase in Saccharomyces cerevisiae, however its mRNA targets have not been mapped on a genome-wide scale. Here we describe a genome-wide approach, RNA immunoprecipitation-high throughput sequencing (RIP-seq), to identify the RNAs bound to Ccr4, and two proteins that associate with it, Dhh1 and Puf5...
November 20, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29158335/a-deconvolution-protocol-for-chip-seq-reveals-analogous-enhancer-structures-on-the-mouse-and-human-ribosomal-rna-genes
#20
Jean-Clement Mars, Marianne Sabourin-Felix, Michel G Tremblay, Tom Moss
The combination of Chromatin Immunoprecipitation and Massively Parallel Sequencing, or ChIP-Seq, has greatly advanced our genome-wide understanding of chromatin and enhancer structures. However, its resolution at any given genetic locus is limited by several factors. In applying ChIP-Seq to the study of the ribosomal RNA genes, we found that a major limitation to resolution was imposed by the underlying variability in sequence coverage that very often dominates the protein-DNA interaction profiles. Here we describe a simple numerical deconvolution approach that in large part corrects for this variability and significantly improves both the resolution and quantitation of protein-DNA interaction maps deduced from ChIP-Seq data...
November 20, 2017: G3: Genes—Genomes—Genetics
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