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RNA folding

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https://www.readbyqxmd.com/read/28341197/label-free-quantitative-proteomics-unravels-the-importance-of-rna-processing-in-glioma-malignancy
#1
Baibin Bi, Feng Li, Jisheng Guo, Cuiling Li, Ruirui Jing, Xin Lv, Xinjun Chen, Fengqin Wang, Kazem M Azadzoi, Lin Wang, Yuguang Liu, Jing-Hua Yang
Glioma, one of the most common cancers in human, is classified to different grades according to the degrees of malignancy. Glioblastoma (GBM) is known to be the most malignant (Grade IV) whereas low-grade astrocytoma (LGA, Grade II) is relatively benign. The mechanism underlying the pathogenesis and progression of glioma malignancy remains unclear. Here we report a quantitative proteomic study to elucidate the differences between GBM and LGA using liquid chromatography and tandem mass spectrometry followed by label-free quantification...
March 21, 2017: Neuroscience
https://www.readbyqxmd.com/read/28340459/transcriptional-profiling-of-porcine-granulosa-cells-exposed-to-2-3-7-8-tetrachlorodibenzo-p-dioxin
#2
Agnieszka Sadowska, Anna Nynca, Monika Ruszkowska, Lukasz Paukszto, Kamil Myszczynski, Karina Orlowska, Sylwia Swigonska, Tomasz Molcan, Jan P Jastrzebski, Renata E Ciereszko
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a toxic man-made chemical compound contaminating the environment. An exposure of living organisms to TCDD may result in numerous disorders, including reproductive pathologies. The aim of the current study was to examine the effects of TCDD on the transcriptome of porcine granulosa cell line AVG-16. By employing next-generation sequencing (NGS) we aimed to identify genes potentially involved in the mechanism of TCDD action and toxicity in porcine granulosa cells...
March 16, 2017: Chemosphere
https://www.readbyqxmd.com/read/28339187/accurate-mirna-analysis-in-crude-cell-lysate-by-capillary-electrophoresis-based-hybridization-assay-in-comparison-with-quantitative-reverse-transcription-polymerase-chain-reaction
#3
Liang Hu, Alexander S Stasheuski, David W Wegman, Nan Wu, Burton B Yang, Heyam Hayder, Chun Peng, Stanley K Liu, George M Yousef, Sergey N Krylov
Accurate quantitation of microRNA (miRNA) in tissue samples is required for validation and clinical use of miRNA-based disease biomarkers. Since sample processing, such as RNA extraction, introduces undesirable biases, it is advantageous to measure miRNA in a crude cell lysate. Here we report on accurate miRNA quantitation in crude cell lysate by a CE-based hybridization assay termed direct quantitative analysis of multiple miRNAs (DQAMmiR). Accuracy and precision of miRNA quantitation were determined for miRNA samples in a crude cell lysate, RNA extract from the lysate, and a pure buffer...
March 24, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28338950/non-replicative-rna-recombination-of-an-animal-plus-strand-rna-virus-in-the-absence-of-efficient-translation-of-viral-proteins
#4
Maximiliane Kleine Büning, Denise Meyer, Sophia Austermann-Busch, Gleyder Roman-Sosa, Tillmann Rümenapf, Paul Becher
RNA recombination is a major driving force for the evolution of RNA viruses and is significantly implicated in the adaptation of viruses to new hosts, changes of virulence, as well as in the emergence of new viruses including drug-resistant and escape mutants. However, the molecular details of recombination in animal RNA viruses are only poorly understood. In order to determine whether viral RNA recombination depends on translation of viral proteins, a non-replicative recombination system was established which is based on cotransfection of cells with synthetic bovine viral diarrhea virus (family Flaviviridae) RNA genome fragments either lacking the internal ribosome entry site required for cap-independent translation or lacking almost the complete polyprotein coding region...
March 11, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28337328/structure-activity-relationship-study-of-ql47-a-broad-spectrum-antiviral-agent
#5
Yanke Liang, Melissanne de Wispelaere, Margot Carocci, Qingsong Liu, Jinhua Wang, Priscilla L Yang, Nathanael S Gray
Here we report the structure-activity relationship (SAR) investigations of QL-XII-47 (QL47), a compound that possesses broad-spectrum antiviral activity against dengue virus and other RNA viruses. A medicinal chemistry campaign initiated from QL47, a previously reported covalent BTK inhibitor, to derive YKL-04-085, which is devoid of any kinase activity when screened against a panel of 468 kinases and with improved pharmacokinetic properties. Both QL47 and YKL-04-085 are potent inhibitors of viral translation and exhibit cellular antiviral activity at 35-fold lower concentrations relative to inhibition of host-cell proliferation...
March 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28336611/self-assembly-of-genetically-encoded-dna-protein-hybrid-nanoscale-shapes
#6
Florian Praetorius, Hendrik Dietz
We describe an approach to bottom-up fabrication that allows integration of the functional diversity of proteins into designed three-dimensional structural frameworks. A set of custom staple proteins based on transcription activator-like effector proteins folds a double-stranded DNA template into a user-defined shape. Each staple protein is designed to recognize and closely link two distinct double-helical DNA sequences at separate positions on the template. We present design rules for constructing megadalton-scale DNA-protein hybrid shapes; introduce various structural motifs, such as custom curvature, corners, and vertices; and describe principles for creating multilayer DNA-protein objects with enhanced rigidity...
March 24, 2017: Science
https://www.readbyqxmd.com/read/28336346/antiviral-activity-of-the-adenosine-analogue-bcx4430-against-west-nile-virus-and-tick-borne-flaviviruses
#7
Luděk Eyer, Darina Zouharová, Jana Širmarová, Martina Fojtíková, Michal Štefánik, Jan Haviernik, Radim Nencka, Erik de Clercq, Daniel Růžek
There are currently no approved antiviral therapies against medically important human flaviviruses. The imino-C-nucleoside BCX4430 shows broad-spectrum antiviral activity against a wide range of RNA viruses. Here, we demonstrate that BCX4430 inhibits tick-borne species of the genus Flavivirus; however, the antiviral effect varies against individual species. Micro-molar BCX4430 levels inhibited tick-borne encephalitis virus (TBEV); while, approximately 3-8-fold higher concentrations were needed to inhibit louping ill virus and Kyasanur Forest disease virus...
March 20, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28336307/measuring-rna-structure-transcriptome-wide-with-icshape
#8
REVIEW
Dalen Chan, Chao Feng, Robert C Spitale
RNA molecules can be found at the heart of nearly every aspect of gene regulation: from gene expression to protein translation. The ability of RNA molecules to fold into intricate structures guides their function. Chemical methods to measure RNA structure have been part of the RNA biologists toolkit for several decades. These methods, although often cumbersome and difficult to perform on large RNAs, are notable for their accuracy and precision of structural measurements. Recent extension of these methods to transcriptome-wide analyses has opened the door to interrogating the structure of complete RNA molecules inside cells...
March 20, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28336124/ultraviolet-b-inhibition-of-dnmt1-activity-via-ahr-activation-dependent-sirt1-suppression-in-cd4-t-cells-from-systemic-lupus-erythematosus-patients
#9
Zhouwei Wu, Xingyu Mei, Zuolin Ying, Yue Sun, Jun Song, Weimin Shi
BACKGROUND: Previous studies have reported that ultraviolet B (UVB) inhibits DNA methyltransferase1 (DNMT1) activity in CD4+ T cells from systemic lupus erythematosus (SLE) patients. Silent mating type information regulation 2 homolog 1 (SIRT1) is a type of Class III histone deacetylases (HDACs), and has been reported to play roles in the pathogenesis of different autoimmune diseases and can modulate DNMT1 activity. Moreover, aryl hydrocarbon receptor (AhR) has been reported to link UVB with SLE...
March 10, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28335556/trm5-and-trmd-two-enzymes-from-distinct-origins-catalyze-the-identical-trna-modification-m%C3%A2-g37
#10
REVIEW
Sakurako Goto-Ito, Takuhiro Ito, Shigeyuki Yokoyama
The N¹-atom of guanosine at position 37 in transfer RNA (tRNA) is methylated by tRNA methyltransferase 5 (Trm5) in eukaryotes and archaea, and by tRNA methyltransferase D (TrmD) in bacteria. The resultant modified nucleotide m¹G37 positively regulates the aminoacylation of the tRNA, and simultaneously functions to prevent the +1 frameshift on the ribosome. Interestingly, Trm5 and TrmD have completely distinct origins, and therefore bear different tertiary folds. In this review, we describe the different strategies utilized by Trm5 and TrmD to recognize their substrate tRNAs, mainly based on their crystal structures complexed with substrate tRNAs...
March 21, 2017: Biomolecules
https://www.readbyqxmd.com/read/28335001/fastkd1-and-fastkd4-have-opposite-effects-on-expression-of-specific-mitochondrial-rnas-depending-upon-their-endonuclease-like-rap-domain
#11
Erik Boehm, Sofia Zaganelli, Kinsey Maundrell, Alexis A Jourdain, Stéphane Thore, Jean-Claude Martinou
FASTK family proteins have been identified as regulators of mitochondrial RNA homeostasis linked to mitochondrial diseases, but much remains unknown about these proteins. We show that CRISPR-mediated disruption of FASTKD1 increases ND3 mRNA level, while disruption of FASTKD4 reduces the level of ND3 and of other mature mRNAs including ND5 and CYB, and causes accumulation of ND5-CYB precursor RNA. Disrupting both FASTKD1 and FASTKD4 in the same cell results in decreased ND3 mRNA similar to the effect of depleting FASTKD4 alone, indicating that FASTKD4 loss is epistatic...
March 10, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334976/a-sensitivity-analysis-of-rna-folding-nearest-neighbor-parameters-identifies-a-subset-of-free-energy-parameters-with-the-greatest-impact-on-rna-secondary-structure-prediction
#12
Jeffrey Zuber, Hongying Sun, Xiaoju Zhang, Iain McFadyen, David H Mathews
Nearest neighbor parameters for estimating the folding energy changes of RNA secondary structures are used in structure prediction and analysis. Despite their widespread application, a comprehensive analysis of the impact of each parameter on the precision of calculations had not been conducted. To identify the parameters with greatest impact, a sensitivity analysis was performed on the 291 parameters that compose the 2004 version of the free energy nearest neighbor rules. Perturbed parameter sets were generated by perturbing each parameter independently...
March 15, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334881/random-pseuoduridylation-in-vivo-reveals-critical-region-of-escherichia-coli-23s-rrna-for-ribosome-assembly
#13
Margus Leppik, Aivar Liiv, Jaanus Remme
Pseudouridine is the most common modified nucleoside in RNA, which is found in stable RNA species and in eukaryotic mRNAs. Functional analysis of pseudouridine is complicated by marginal effect of its absence. We demonstrate that excessive pseudouridines in rRNA inhibit ribosome assembly. Ten-fold increase of pseudouridines in the 16S and 23S rRNA made by a chimeric pseudouridine synthase leads to accumulation of the incompletely assembled large ribosome subunits. Hyper modified 23S rRNA is found in the r-protein assembly defective particles and are selected against in the 70S and polysome fractions showing modification interference...
March 7, 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
#14
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/28334779/targeted-gene-knock-in-by-homology-directed-genome-editing-using-cas9-ribonucleoprotein-and-aav-donor-delivery
#15
Thomas Gaj, Brett T Staahl, Gonçalo M C Rodrigues, Prajit Limsirichai, Freja K Ekman, Jennifer A Doudna, David V Schaffer
Realizing the full potential of genome editing requires the development of efficient and broadly applicable methods for delivering programmable nucleases and donor templates for homology-directed repair (HDR). The RNA-guided Cas9 endonuclease can be introduced into cells as a purified protein in complex with a single guide RNA (sgRNA). Such ribonucleoproteins (RNPs) can facilitate the high-fidelity introduction of single-base substitutions via HDR following co-delivery with a single-stranded DNA oligonucleotide...
March 2, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334186/rnascclust-clustering-rna-sequences-using-structure-conservation-and-graph-based-motifs
#16
Milad Miladi, Alexander Junge, Fabrizio Costa, Stefan E Seemann, Jakob Hull Havgaard, Jan Gorodkin, Rolf Backofen
Motivation: Clustering RNA sequences with common secondary structure is an essential step towards studying RNA function. Whereas structural RNA alignment strategies typically identify common structure for orthologous structured RNAs, clustering seeks to group paralogous RNAs based on structural similarities. However, existing approaches for clustering paralogous RNAs, do not take the compensatory base pair changes obtained from structure conservation in orthologous sequences into account...
February 27, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28333132/enzyme-iia-ntr-regulates-salmonella-invasion-via-1-2-propanediol-and-propionate-catabolism
#17
Woongjae Yoo, Dajeong Kim, Hyunjin Yoon, Sangryeol Ryu
Many Proteobacteria possess a nitrogen-metabolic phosphotransferase system (PTS(Ntr)) consisting of EI(Ntr), NPr, and EIIA(Ntr) (encoded by ptsP, ptsO, and ptsN, respectively). The PTS(Ntr) plays diverse regulatory roles, but the substrate phosphorylated by EIIA(Ntr) and its primary functions have not yet been identified. To comprehensively understand the roles of PTS(Ntr) in Salmonella Typhimurium, we compared the whole transcriptomes of wild-type and a ΔptsN mutant. Genome-wide RNA sequencing revealed that 3...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28332609/global-preamplification-simplifies-targeted-mrna-quantification
#18
Thomas Kroneis, Emma Jonasson, Daniel Andersson, Soheila Dolatabadi, Anders Ståhlberg
The need to perform gene expression profiling using next generation sequencing and quantitative real-time PCR (qPCR) on small sample sizes and single cells is rapidly expanding. However, to analyse few molecules, preamplification is required. Here, we studied global and target-specific preamplification using 96 optimised qPCR assays. To evaluate the preamplification strategies, we monitored the reactions in real-time using SYBR Green I detection chemistry followed by melting curve analysis. Next, we compared yield and reproducibility of global preamplification to that of target-specific preamplification by qPCR using the same amount of total RNA...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28331847/learning-parsimonious-classification-rules-from-gene-expression-data-using-bayesian-networks-with-local-structure
#19
Jonathan Lyle Lustgarten, Jeya Balaji Balasubramanian, Shyam Visweswaran, Vanathi Gopalakrishnan
The comprehensibility of good predictive models learned from high-dimensional gene expression data is attractive because it can lead to biomarker discovery. Several good classifiers provide comparable predictive performance but differ in their abilities to summarize the observed data. We extend a Bayesian Rule Learning (BRL-GSS) algorithm, previously shown to be a significantly better predictor than other classical approaches in this domain. It searches a space of Bayesian networks using a decision tree representation of its parameters with global constraints, and infers a set of IF-THEN rules...
March 2017: Data (Basel)
https://www.readbyqxmd.com/read/28331057/upregulation-of-distinct-collagen-transcripts-in-post-surgery-scar-tissue-a-study-of-conjunctival-fibrosis
#20
Li-Fong Seet, Li Zhen Toh, Stephanie W L Chu, Sharon N Finger, Jocelyn L L Chua, Tina T Wong
Excessive accumulation of collagen is often used to assess the development of fibrosis. This study aims to identify collagen genes that define fibrosis in the conjunctiva following glaucoma filtration surgery (GFS). Using the mouse model of GFS, we have identified collagen transcripts that were upregulated in the fibrotic phase of wound healing via RNA-seq. The top three highest induced collagen transcripts belong to Col8a1, Col11a1 and Col8a2 Further validation of the Col8a1, Col11a1 and Col8a2 transcripts revealed their increase by 67-, 54- and 18-folds respectively in the fibrotic phase, compared to 12-fold for Col1a1, the most commonly evaluated collagen gene for fibrosis...
March 22, 2017: Disease Models & Mechanisms
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