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https://www.readbyqxmd.com/read/28317959/packing-energetics-determine-the-folding-routes-of-the-rnase-h-proteins
#1
Shilpa Yadahalli, Shachi Gosavi
Comparative studies of proteins from a family have been used to understand the factors that determine the folding routes of proteins. It has been conjectured that the folding mechanism of ribonuclease-H (RNase-H) proteins is determined by the topology of their fold. To test this hypothesis, we computationally studied the folding of four proteins from the RNase-H family, which have the overall RNase-H fold, but whose topologies differ in the region termed CORE in E. coli RNase-H. We simulated the folding of these proteins using molecular dynamics (MD) simulations of a coarse-grained structure-based model (SBM) which captures the effects of topology and found that the four proteins had similar folding routes...
March 20, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28306242/excision-repair-initiated-enzyme-assisted-bicyclic-cascade-signal-amplification-for-ultrasensitive-detection-of-uracil-dna-glycosylase
#2
Li-Juan Wang, Ming Ren, Qianyi Zhang, Bo Tang, Chun-Yang Zhang
Uracil-DNA glycosylase (UDG) is an important base excision repair (BER) enzyme responsible for the repair of uracil-induced DNA lesion and the maintenance of genomic integrity, while the aberrant expression of UDG is associated with a variety of cancers. Thus the accurate detection of UDG activity is essential to biomedical research and clinical diagnosis. Here, we develop a fluorescent method for ultrasensitive detection of UDG activity using excision repair-initiated enzyme-assisted bicyclic cascade signal amplification...
March 17, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28302473/quantitative-relationship-between-chemical-properties-and-bioactivities-of-anti-microrna-oligonucleotides-targeted-to-tumor-associated-microrna-21
#3
Koji Nagahama, Kenta Iseda, Daichi Kawano, Junji Kawakami
Synthetic anti-microRNA oligonucleotides (AMOs) are promising drug candidates to inactivate disease-related microRNAs because of their sequence-specific binding to their targets and the variety of chemical modifications available. Over the last decade, the qualitative relationships between the chemical properties of AMOs and bioactivity (inactivation of their target miRNAs) have been studied to enhance their bioactivity. On the other hand, in real-world drug development, drugs must be designed case-by-case, taking many factors into account...
March 13, 2017: Biochimie
https://www.readbyqxmd.com/read/28299484/characterization-of-a-new-badnavirus-from-wisteria-sinensis
#4
Yongqiang Li, Congliang Deng, Yan Qiao, Xiaoli Zhao, Qi Zhou
The complete genome sequence of a previously undescribed badnavirus isolated from a wisteria plant exhibiting mosaic and crinkle symptoms in Beijing, China, was determined. The circular double-stranded DNA genome of this virus was 7362 bp in size with four open reading frames (ORFs 1 to 4) on the plus strand. Sequence analysis showed that this virus shared the highest (69%) nucleotide (nt) sequence identity with pagoda yellow mosaic associated virus (PYMAV). In the RT-RNase H region of the ORF-3 encoded polyprotein, this virus shared 74% nt sequence identity with PYMAV...
March 15, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28298445/the-structure-and-function-of-mycobacterium-tuberculosis-mazf-mt6-provides-insights-into-conserved-features-of-mazf-endonucleases
#5
Eric D Hoffer, Stacey J Miles, Christine M Dunham
Toxin-antitoxin systems are ubiquitous in prokaryotic and archaea genomes and regulate growth in response to stress. E. coli contains at least 36 putative toxin-antitoxin gene pairs, and some pathogens such as Mycobacterium tuberculosis (Mtb) have over 90 toxin-antitoxin operons. E. coli MazF cleaves free mRNA after encountering stress and nine Mtb MazF family members cleave mRNA, tRNA, or rRNA. Moreover, Mtb MazF-mt6 cleaves 23S rRNA Helix 70 to inhibit protein synthesis. The overall tertiary folds of these MazFs are predicted to be similar, therefore it is unclear how they recognize structurally distinct RNAs...
March 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28292248/surface-engineered-dendrimers-in-sirna-delivery-and-gene-silencing
#6
Vishakha Tambe, Shreya Thakkar, Nidhi Raval, Dilip Sharma, Kiran Kalia, Rakesh Kumar Tekade
BACKGROUND: Therapeutic efficacy of dreadful diseases like cancer, HIV (Human Immunodeficiency Virus) can be enhanced by delivering molecules which regulate function at gene level rather than at receptor level. Silencing RNA is one such approach recently used to silence target gene expressed diseases; and thereby reduce target protein levels. Many of the non-viral vectors are proved to act as carriers for silencing RNA. Dendrimers being one of them have less size, low poly dispersibility index, water solubility, multivalence, and easy surface modification...
March 14, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28287718/regulating-mirna-21-biogenesis-by-bi-functional-small-molecules
#7
Hao Yan, Umesh Bhattarai, Zhi-Fo Guo, Fu-Sen Liang
MicroRNAs (miRNAs) are non-coding RNAs that regulate translation by targeting mRNAs. In their biogenesis, precursor miRNAs (pre-miRNAs) are cleaved by RNase Dicer to give mature miRNAs. Herein, we report a new strategy to regulate miRNA biogenesis by using bi-functional small molecules that block Dicer catalyzed pre-miRNA cleavage. The bi-functional molecules consist of a pre-miRNA binding unit connected by a linker to a Dicer inhibiting unit. Recognition of a target pre-miRNA by the RNA binding unit brings the Dicer inhibitor unit into close proximity to the pre-miRNA cleavage site where it inhibits Dicer...
March 13, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28285458/applications-and-advantages-of-stable-isotope-phosphate-labeling-of-rna-in-mass-spectrometry
#8
REVIEW
Kayla Borland, Patrick A Limbach
Mass spectrometry (MS) has become an enabling technology for the characterization of post-transcriptionally modified nucleosides within ribonucleic acids (RNAs). These modified RNAs tend to be more challenging to completely characterize using conventional genomic-based sequencing technologies. As with many biological molecules, information relating to the presence or absence of a particular compound (i.e., qualitative measurement) is only one step in sample characterization. Additional useful information is found by performing quantitative measurements on the levels of the compound of interest in the sample...
April 2017: Topics in Current Chemistry (Journal)
https://www.readbyqxmd.com/read/28283321/minimized-natural-versions-of-fungal-ribotoxins-show-improved-active-site-plasticity
#9
Moisés Maestro-López, Miriam Olombrada, Lucía García-Ortega, Daniel Serrano-González, Javier Lacadena, Mercedes Oñaderra, José G Gavilanes, Álvaro Martínez-Del-Pozo
Fungal ribotoxins are highly specific extracellular RNases which cleave a single phosphodiester bond at the ribosomal sarcin-ricin loop, inhibiting protein biosynthesis by interfering with elongation factors. Most ribotoxins show high degree of conservation, with similar sizes and amino acid sequence identities above 85%. Only two exceptions are known: hirsutellin A and anisoplin, produced by the entomopathogenic fungi Hirsutella thompsonii and Metarhizium anisopliae, respectively. Both proteins are similar but smaller than the other known ribotoxins (130 vs 150 amino acids), displaying only about 25% sequence identity with them...
March 7, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28282218/immunotoxins-in-cancer-therapy-review-and-update
#10
Bahman Akbari, Safar Farajnia, Shiva Ahdi Khosroshahi, Fatemeh Safari, Mohammadreza Yousefi, Hassan Dariushnejad, Leila Rahbarnia
Immunotoxins are a novel class of cancer therapeutics that contains a cytotoxic agent fused to a targeting moiety. Various toxic agents from different sources are used in immunotoxin development, including bacterial, plant and human origin cytotoxic elements. Although bacterial and plant-derived toxins are highly toxic and commonly used in immunotoxins, their immunogenicity for human restricted their application in cancer therapy. Here, we discuss the advantages and limitations of bacterial toxins such as Pseudomonas and Diphtheria toxins, plant toxins such as ricin and gelonin, and some endogenous protein of human origin such as RNases and Granzymes...
March 1, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/28281253/microrna-biosensing-with-two-dimensional-surface-plasmon-resonance-imaging
#11
Ho Pui Ho, Fong Chuen Loo, Shu Yuen Wu, Dayong Gu, Ken-Tye Yong, Siu Kai Kong
Two-dimensional surface plasmon resonance (2D-SPR) imaging, which provides a real-time, sensitive, and high-throughput analysis of surface events in a two dimensional manner, is a valuable tool for studying biomolecular interactions and biochemical reactions without using any tag labels. The sensing principle of 2D-SPR includes angular, wavelength, and phase interrogation. In this chapter, the 2D-SPR imaging technique is applied for sensing a target microRNA by its corresponding oligonucleotide probes, with sequence complementarity, immobilized on the gold SPR sensing surface...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28278290/exosomes-are-released-by-bystander-cells-exposed-to-radiation-induced-biophoton-signals-reconciling-the-mechanisms-mediating-the-bystander-effect
#12
Michelle Le, Cristian Fernandez-Palomo, Fiona E McNeill, Colin B Seymour, Andrew J Rainbow, Carmel E Mothersill
OBJECTIVE: The objective of our study was to explore a possible molecular mechanism by which ultraviolet (UV) biophotons could elicit bystander responses in reporter cells and resolve the problem of seemingly mutually exclusive mechanisms of a physical UV signal & a soluble factor-mediated bystander signal. METHODS: The human colon carcinoma cell line, HCT116 p53 +/+, was directly irradiated with 0.5 Gy tritium beta particles to induce ultraviolet biophoton emission...
2017: PloS One
https://www.readbyqxmd.com/read/28278199/monitoring-integrity-and-localization-of-modified-single-stranded-rna-oligonucleotides-using-ultrasensitive-fluorescence-methods
#13
Philipp Heissig, Waldemar Schrimpf, Philipp Hadwiger, Ernst Wagner, Don C Lamb
Short single-stranded oligonucleotides represent a class of promising therapeutics with diverse application areas. Antisense oligonucleotides, for example, can interfere with various processes involved in mRNA processing through complementary base pairing. Also RNA interference can be regulated by antagomirs, single-stranded siRNA and single-stranded microRNA mimics. The increased susceptibility to nucleolytic degradation of unpaired RNAs can be counteracted by chemical modification of the sugar phosphate backbone...
2017: PloS One
https://www.readbyqxmd.com/read/28277930/wobble-uridine-modifications-a-reason-to-live-a-reason-to-die
#14
Raffael Schaffrath, Sebastian A Leidel
Wobble uridines (U34) are generally modified in all species. U34 modifications can be essential in metazoans but are not required for viability in fungi. In this review, we provide an overview on the types of modifications and how they affect the physico-chemical properties of wobble uridines. We describe the molecular machinery required to introduce these modifications into tRNA posttranscriptionally and discuss how posttranslational regulation may affect the activity of the modifying enzymes. We highlight the activity of anticodon specific RNases that target U34 containing tRNA...
February 23, 2017: RNA Biology
https://www.readbyqxmd.com/read/28277929/both-exo-and-endo-nucleolytic-activities-of-rnase-j1-from-staphylococcus-aureus-are-manganese-dependent-and-active-on-triphosphorylated-5-ends
#15
Stéphane Hausmann, Vanessa Andrade Guimarães, Dominique Garcin, Natalia Baumann, Patrick Linder, Peter Redder
RNA decay and RNA maturation are important steps in the regulation of bacterial gene expression. RNase J, which is present in about half of bacterial species, has been shown to possess both endo- and 5' to 3' exo-ribonuclease activities. The exonucleolytic activity is clearly involved in the degradation of mRNA and in the maturation of at least the 5'end of 16S rRNA in the two Firmicutes Staphylococcus aureus and Bacillus subtilis. The endoribonuclease activity of RNase J from a number of species has been shown to be weak in vitro and 3-D structural data of different RNase J orthologs has not provided a clear explanation for the molecular basis of this activity...
March 1, 2017: RNA Biology
https://www.readbyqxmd.com/read/28276031/analysis-of-mitochondrial-rna-processing-defects-in-patient-derived-tissues-by-qrt-pcr-and-rnaseq
#16
Robert Kopajtich, Johannes A Mayr, Holger Prokisch
Transcription of the mitochondrial genome yields three large polycistronic transcripts that undergo multiple endonucleolytic processing steps, before resulting in functional mRNAs, tRNAs, and rRNAs. Cleavage of the large precursor transcripts is mainly performed by the RNase P complex and RNase Z that cleave mitochondrial pre-tRNAs at their 5' and 3' ends respectively. Most likely there are additional enzymes involved that still await identification and characterization. Defects in mitochondrial RNA processing have been associated with human disease...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28271277/sequence-specific-backbone-resonance-assignments-and-microsecond-timescale-molecular-dynamics-simulation-of-human-eosinophil-derived-neurotoxin
#17
Donald Gagné, Chitra Narayanan, Khushboo Bafna, Laurie-Anne Charest, Pratul K Agarwal, Nicolas Doucet
Eight active canonical members of the pancreatic-like ribonuclease A (RNase A) superfamily have been identified in human. All structural homologs share similar RNA-degrading functions, while also cumulating other various biological activities in different tissues. The functional homologs eosinophil-derived neurotoxin (EDN, or RNase 2) and eosinophil cationic protein (ECP, or RNase 3) are known to be expressed and secreted by eosinophils in response to infection, and have thus been postulated to play an important role in host defense and inflammatory response...
March 7, 2017: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/28268090/both-r-loop-removal-and-ribonucleotide-excision-repair-activities-of-rnase-h2-contribute-substantially-to-chromosome-stability
#18
Deborah A Cornelio, Hailey N C Sedam, Jessica A Ferrarezi, Nadia M V Sampaio, Juan Lucas Argueso
Cells carrying deletions of genes encoding H-class ribonucleases display elevated rates of chromosome instability. The role of these enzymes is to remove RNA-DNA associations including persistent mRNA-DNA hybrids (R-loops) formed during transcription, and ribonucleotides incorporated into DNA during replication. RNases H1 and H2 can degrade the RNA component of R-loops, but only RNase H2 can initiate accurate ribonucleotide excision repair (RER). In order to examine the specific contributions of these activities to chromosome stability, we measured rates of loss-of-heterozygosity (LOH) in diploid Saccharomyces cerevisiae yeast strains carrying the rnh201-RED separation-of-function allele, encoding a version of RNase H2 that is RER-defective, but partly retains its other activity...
February 20, 2017: DNA Repair
https://www.readbyqxmd.com/read/28267794/the-interdependencies-of-viral-load-the-innate-immune-response-and-clinical-outcome-in-children-presenting-to-the-emergency-department-with-respiratory-syncytial-virus-associated-bronchiolitis
#19
Felipe-Andrés Piedra, Minghua Mei, Vasanthi Avadhanula, Reena Mehta, Letisha Aideyan, Roberto P Garofalo, Pedro A Piedra
Respiratory syncytial virus (RSV) causes significant infant morbidity and mortality. For decades severe RSV-induced disease was thought to result from an uncontrolled host response to viral replication, but recent work suggests that a strong innate immune response early in infection is protective. To shed light on host-virus interactions and the viral determinants of disease, copy numbers of five RSV genes (NS1, NS2, N, G, F) were measured by quantitative real-time polymerase chain reaction (qPCR) in nasal wash samples from children with RSV-associated bronchiolitis...
2017: PloS One
https://www.readbyqxmd.com/read/28258464/sequential-fragment-ion-filtering-and-endoglycosidase-assisted-identification-of-intact-glycopeptides
#20
Zixiang Yu, Xinyuan Zhao, Fang Tian, Yang Zhao, Yong Zhang, Yi Huang, Xiaohong Qian, Wantao Ying
Detailed characterization of glycoprotein structures requires determining both the sites of glycosylation as well as the glycan structures associated with each site. In this work, we developed an analytical strategy for characterization of intact N-glycopeptides in complex proteome samples. In the first step, tryptic glycopeptides were enriched using ZIC-HILIC. Secondly, a portion of the glycopeptides was treated with endoglycosidase H (Endo H) to remove high-mannose (Man) and hybrid N-linked glycans. Thirdly, a fraction of the Endo H-treated glycopeptides was further subjected to PNGase F treatment in (18)O water to remove the remaining complex glycans...
March 3, 2017: Analytical and Bioanalytical Chemistry
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