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https://www.readbyqxmd.com/read/28108656/functionally-interdependent-shape-switching-nanoparticles-with-controllable-properties
#1
Justin R Halman, Emily Satterwhite, Brandon Roark, Morgan Chandler, Mathias Viard, Anna Ivanina, Eckart Bindewald, Wojciech K Kasprzak, Martin Panigaj, My N Bui, Jacob S Lu, Johann Miller, Emil F Khisamutdinov, Bruce A Shapiro, Marina A Dobrovolskaia, Kirill A Afonin
We introduce a new concept that utilizes cognate nucleic acid nanoparticles which are fully complementary and functionally-interdependent to each other. In the described approach, the physical interaction between sets of designed nanoparticles initiates a rapid isothermal shape change which triggers the activation of multiple functionalities and biological pathways including transcription, energy transfer, functional aptamers and RNA interference. The individual nanoparticles are not active and have controllable kinetics of re-association and fine-tunable chemical and thermodynamic stabilities...
January 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28107630/2-o-methyl-5-hydroxymethylcytidine-a-second-oxidative-derivative-of-5-methylcytidine-in-rna
#2
Sabrina M Huber, Pieter van Delft, Arun A Tanpure, Eric A Miska, Shankar Balasubramanian
5-hydroxymethylcytidine (hm5C) was recently identified as a direct metabolite of m5C in RNA. We investigated the stability of hm5C in human cells using bio-isotopomers and high-resolution tandem LC-MS/MS. This has led to the discovery of a second oxidative metabolite of m5C in RNA, namely 2'-O-methyl-5-hydroxymethylcytidine (hm5Cm). Subsequent quantitative analysis of total RNA from higher organisms, revealed varying levels and TET-independent formation of this new RNA modification.
January 20, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28106744/oligonucleotide-therapy-for-obstructive-and-restrictive-respiratory-diseases
#3
REVIEW
Wupeng Liao, Jinrui Dong, Hong Yong Peh, Lay Hong Tan, Kah Suan Lim, Li Li, Wai-Shiu Fred Wong
Inhaled oligonucleotide is an emerging therapeutic modality for various common respiratory diseases, including obstructive airway diseases like asthma and chronic obstructive pulmonary disease (COPD) and restrictive airway diseases like idiopathic pulmonary fibrosis (IPF). The advantage of direct accessibility for oligonucleotide molecules to the lung target sites, bypassing systemic administration, makes this therapeutic approach promising with minimized potential systemic side effects. Asthma, COPD, and IPF are common chronic respiratory diseases, characterized by persistent airway inflammation and dysregulated tissue repair and remodeling, although each individual disease has its unique etiology...
January 17, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28106731/hypoxia-inducible-factor-1%C3%AE-promotes-endogenous-adaptive-response-in-rat-model-of-chronic-cerebral-hypoperfusion
#4
Ying Yang, Jieyang Ju, Min Deng, Jing Wang, Hui Liu, Li Xiong, Junjian Zhang
Hypoxia inducible factor 1α (HIF-1α), a pivotal regulator of gene expression in response to hypoxia and ischemia, is now considered to regulate both pro-survival and pro-death responses depending on the duration and severity of the stress. We previously showed that chronic global cerebral hypoperfusion (CCH) triggered long-lasting accumulation of HIF-1α protein in the hippocampus of rats. However, the role of the stabilized HIF-1α in CCH is obscure. Here, we knock down endogenous HIF-1α to determine whether and how HIF-1α affects the disease processes and phenotypes of CCH...
January 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28104569/interaction-of-octahedral-ruthenium-ii-polypyridyl-complex-ru-bpy-2-pip-2-with-poly-u-%C3%A2-poly-a-poly-u-triplex-increasing-third-strand-stabilization-of-the-triplex-without-affecting-the-stability-of-the-duplex
#5
Zhiyuan Zhu, Mengna Peng, Jingwen Zhang, Lifeng Tan
Triple-helical RNA are of interest because of possible biological roles as well as the potential therapeutic uses of these structures, while the stability of triplexes is usually weaker than that of the Watson-Crick base pairing duplex strand due to the electrostatic repulsion between three polyanionic strands. Therefore, how to increase the stability of the specific sequences of triplexes are of importance. In this paper the binding of a Ru(II) complex, [Ru(bpy)2(PIP)](2+) (bpy=2.2'-bipyridine, PIP=2-phenyl-1H-imidazo[4,5-f]- [1,10]-phenanthroline), with poly(U)·poly(A)*poly(U) triplex has been investigated by spectrophotometry, spectrofluorometry, viscosimetry and circular dichroism...
January 4, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28102930/modulation-of-the-thermodynamic-signatures-of-an-rna-thermometer-by-osmolytes-and-salts
#6
Mimi Gao, Loana Arns, Roland Winter
Folding of ribonucleic acids (RNAs) is driven by several factors, such as base pairing and stacking, chain entropy, and ion-mediated electrostatics, which have been studied in great detail. However, the power of background molecules in the cellular milieu is often neglected. Herein, we study the effect of common osmolytes on the folding equilibrium of a hairpin-structured RNA and, using pressure perturbation, provide novel thermodynamic and volumetric insights into the modulation mechanism. The presence of TMAO causes an increased thermal stability and a more positive volume change for the helix-to-coil transition, whereas urea destabilizes the hairpin and leads to an increased expansibility of the unfolded state...
January 19, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28102760/phf13-a-new-player-involved-in-rna-polymerase-ii-transcriptional-regulation-and-co-transcriptional-splicing
#7
Alisa Fuchs, Marcos Torroba, Sarah Kinkley
We recently identified PHF13 as an H3K4me2/3 chromatin reader and transcriptional co-regulator. We found that PHF13 interacts with RNAPIIS5P and PRC2 stabilizing their association with active and bivalent promoters. Furthermore, mass spectrometry analysis identified ∼50 spliceosomal proteins in PHF13's interactome. Here we will discuss the potential role of PHF13 in RNAPII pausing and co-transcriptional splicing.
January 19, 2017: Transcription
https://www.readbyqxmd.com/read/28101966/the-free-energy-of-locking-a-ring-changing-a-deoxyribonucleoside-to-a-locked-nucleic-acid
#8
You Xu, Alessandra Villa, Lennart Nilsson
Locked nucleic acid (LNA), a modified nucleoside which contains a bridging group across the ribose ring, improves the stability of DNA/RNA duplexes significantly, and therefore is of interest in biotechnology and gene therapy applications. In this study, we investigate the free energy change between LNA and DNA nucleosides. The transformation requires the breaking of the bridging group across the ribose ring, a problematic transformation in free energy calculations. To address this, we have developed a 3-step (easy to implement) and a 1-step protocol (more efficient, but more complicated to setup), for single and dual topologies in classical molecular dynamics simulations, using the Bennett Acceptance Ratio method to calculate the free energy...
January 19, 2017: Journal of Computational Chemistry
https://www.readbyqxmd.com/read/28101374/arginine-methylation-of-usp9x-promotes-its-interaction-with-tdrd3-and-its-anti-apoptotic-activities-in-breast-cancer-cells
#9
Nithya Narayanan, Zhihao Wang, Ling Li, Yanzhong Yang
The Tudor domain-containing proteins are characterized by their specific interactions with methylated protein motifs, including methyl-arginines and methyl-lysines. The Tudor domain-containing protein 3 (TDRD3) is one of the major methyl-arginine effector molecules that recognizes methylated arginine residues on histones and the C-terminal domain of RNA polymerase II, and activates transcription. However, majority of the cellular TDRD3 localizes to the cytoplasm and its functions there are still elusive. Here, we have identified ubiquitin-specific protease 9 X-linked (USP9X) as a TDRD3-interacting protein by GST (glutathione S-transferase) pull-down and co-immunoprecipitation...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28101309/patients-with-haemoglobinopathies-and-chronic-hepatitis-c-a-real-difficult-to-treat-population-in-2016
#10
Kalliopi Zachou, Pinelopi Arvaniti, Nikolaos K Gatselis, Kalliopi Azariadis, Georgia Papadamou, Eirini Rigopoulou, George N Dalekos
BACKGROUND & OBJECTIVES: In the past, patients with haemoglobinopathies were at high risk of acquiring hepatitis C virus (HCV) due to multiple transfusions before HCV screening. In these patients, the coexistence of haemochromatosis and chronic hepatitis C (CHC) often leads to more severe liver disease. We assessed the HCV prevalence, clinical characteristics and outcome in this setting with particular attention to the response to treatment including therapies with the new direct acting antivirals (DAAs)...
2017: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/28098827/shared-sulfur-mobilization-routes-for-trna-thiolation-and-molybdenum-cofactor-biosynthesis-in-prokaryotes-and-eukaryotes
#11
REVIEW
Silke Leimkühler, Martin Bühning, Lena Beilschmidt
Modifications of transfer RNA (tRNA) have been shown to play critical roles in the biogenesis, metabolism, structural stability and function of RNA molecules, and the specific modifications of nucleobases with sulfur atoms in tRNA are present in pro- and eukaryotes. Here, especially the thiomodifications xm⁵s²U at the wobble position 34 in tRNAs for Lys, Gln and Glu, were suggested to have an important role during the translation process by ensuring accurate deciphering of the genetic code and by stabilization of the tRNA structure...
January 14, 2017: Biomolecules
https://www.readbyqxmd.com/read/28098820/applying-human-adar1p110-and-adar1p150-for-site-directed-rna-editing-g-c-substitution-stabilizes-guidernas-against-editing
#12
Madeleine Heep, Pia Mach, Philipp Reautschnig, Jacqueline Wettengel, Thorsten Stafforst
Site-directed RNA editing is an approach to reprogram genetic information at the RNA level. We recently introduced a novel guideRNA that allows for the recruitment of human ADAR2 to manipulate genetic information. Here, we show that the current guideRNA design is already able to recruit another human deaminase, ADAR1, in both isoforms, p110 and p150. However, further optimization seems necessary as the current design is less efficient for ADAR1 isoforms. Furthermore, we describe hotspots at which the guideRNA itself is edited and show a way to circumvent this auto-editing without losing editing efficiency at the target...
January 14, 2017: Genes
https://www.readbyqxmd.com/read/28098815/replication-fork-protection-factors-controlling-r-loop-bypass-and-suppression
#13
REVIEW
Emily Yun-Chia Chang, Peter C Stirling
Replication-transcription conflicts have been a well-studied source of genome instability for many years and have frequently been linked to defects in RNA processing. However, recent characterization of replication fork-associated proteins has revealed that defects in fork protection can directly or indirectly stabilize R-loop structures in the genome and promote transcription-replication conflicts that lead to genome instability. Defects in essential DNA replication-associated activities like topoisomerase, or the minichromosome maintenance (MCM) helicase complex, as well as fork-associated protection factors like the Fanconi anemia pathway, both appear to mitigate transcription-replication conflicts...
January 14, 2017: Genes
https://www.readbyqxmd.com/read/28096055/an-ancient-family-of-rna-binding-proteins-still-important
#14
REVIEW
Melissa L Wells, Lalith Perera, Perry J Blackshear
RNA-binding proteins are important modulators of mRNA stability, a crucial process that determines the ultimate cellular levels of mRNAs and their encoded proteins. The tristetraprolin (TTP) family of RNA-binding proteins appeared early in the evolution of eukaryotes, and has persisted in modern eukaryotes. The domain structures and biochemical functions of family members from widely divergent lineages are remarkably similar, but their mRNA 'targets' can be very different, even in closely related species. Recent gene knockout studies in species as distantly related as plants, flies, yeasts, and mice have demonstrated crucial roles for these proteins in a wide variety of physiological processes...
January 14, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28095716/circrnas-a-regulator-of-cellular-stress
#15
Joseph W Fischer, Anthony K L Leung
Circular RNAs (CircRNAs) were first identified as a viroid and later found to also be an endogenous RNA splicing product in eukaryotes. In recent years, a series of RNA-sequencing analyses from a diverse range of eukaryotes have shed new light on these eukaryotic circRNAs, revealing dynamic expression patterns in various developmental stages and physiological conditions. In this review, we focus on circRNAs implicated in stress response pathways and explore potential mechanisms underlying their regulation. To date, circRNAs have been shown to act as scaffolds in the assembly of protein complexes, sequester proteins from native subcellular localization, activate transcription of parental genes, inhibit RNA-protein interactions, and function as regulators of microRNA activity...
January 17, 2017: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28094300/sequestration-of-prmt1-and-nd1-l-mrna-into-als-linked-fus-mutant-r521c-positive-aggregates-contributes-to-neurite-degeneration-upon-oxidative-stress
#16
Mi-Hee Jun, Hyun-Hee Ryu, Yong-Woo Jun, Tongtong Liu, Yan Li, Chae-Seok Lim, Yong-Seok Lee, Bong-Kiun Kaang, Deok-Jin Jang, Jin-A Lee
Mutations in fused in sarcoma (FUS), a DNA/RNA binding protein, are associated with familial amyotrophic lateral sclerosis (ALS). However, little is known about how ALS-causing mutations alter protein-protein and protein-RNA complexes and contribute to neurodegeneration. In this study, we identified protein arginine methyltransferase 1 (PRMT1) as a protein that more avidly associates with ALS-linked FUS-R521C than with FUS-WT (wild type) or FUS-P525L using co-immunoprecipitation and LC-MS analysis. Abnormal association between FUS-R521C and PRMT1 requires RNA, but not methyltransferase activity...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28093325/gold-nanostar-polymer-hybrids-for-sirna-delivery-polymer-design-towards-colloidal-stability-and-in-vitro-studies-on-breast-cancer-cells
#17
Carla Sardo, Barbara Bassi, Emanuela F Craparo, Cinzia Scialabba, Elisa Cabrini, Giacomo Dacarro, Agnese D'Agostino, Angelo Taglietti, Gaetano Giammona, Piersandro Pallavicini, Gennara Cavallaro
To overcome the low bioavailability of siRNA (small interfering RNA) and to improve their transfection efficiency, the use of non-viral delivery carriers is today a feasible approach to transform the discovery of these incredibly potent and versatile drugs into clinical practice. Polymer-modified gold nanoconstructs (AuNCs) are currently viewed as efficient and safe intracellular delivery carriers for siRNA, as they have the possibility to conjugate the ability to stably entrap and deliver siRNAs inside cells with the advantages of gold nanoparticles, which can act as theranostic agents and radiotherapy enhancers through laser-induced hyperthermia...
January 16, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28092499/nanoparticles-for-sirna-based-gene-silencing-in-tumor-therapy
#18
Anish Babu, Ranganayaki Muralidharan, Narsireddy Amreddy, Meghna Mehta, Anupama Munshi, Rajagopal Ramesh
Gene silencing through RNA interference (RNAi) has emerged as a potential strategy in manipulating cancer causing genes by complementary base-pairing mechanism. Small interfering RNA (siRNA) is an important RNAi tool that has found significant application in cancer therapy. However due to lack of stability, poor cellular uptake and high probability of loss-of-function due to degradation, siRNA therapeutic strategies seek safe and efficient delivery vehicles for in vivo applications. The current review discusses various nanoparticle systems currently used for siRNA delivery for cancer therapy, with emphasis on liposome based gene delivery systems...
December 2016: IEEE Transactions on Nanobioscience
https://www.readbyqxmd.com/read/28091639/gold-nanoparticles-stabilized-by-cationic-carbosilane-dendrons-synthesis-and-biological-properties
#19
Cornelia E Peña-González, Elzbieta Pedziwiatr-Werbicka, Dzmitry Shcharbin, Carlos Guerrero-Beltrán, Viktar Abashkin, Svetlana Loznikova, José L Jiménez, M Ángeles Muñoz-Fernández, Maria Bryszewska, Rafael Gómez, Javier Sánchez-Nieves, F Javier de la Mata
Gold nanoparticles (AuNPs) and polycationic macromolecules are used as gene carriers. Their behaviour is dependent on several factors, such as the size and type of the framework, charge, etc. We have combined both types of systems and prepared AuNPs covered with cationic carbosilane dendrons with the aim to evaluate their biocompatibility. Water soluble dendronized cationic AuNPs were prepared following a straightforward procedure from dendrons, a gold precursor and a reducing agent in water and were characterized by (1)H NMR, transmission electron microscopy (TEM), dynamic light scattering (DLS), thermogravimetric analysis (TGA), ultraviolet spectroscopy (UV), and zeta potential (ZP)...
January 16, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28090303/genotype-phenotype-effects-of-bmpr2-mutations-on-disease-severity-in-mouse-models-of-pulmonary-hypertension
#20
Andrea L Frump, Arunima Datta, Sampa Ghose, James West, Mark P de Caestecker
More than 350 mutations in the type-2 BMP (bone morphogenetic protein) receptor, BMPR2, have been identified in patients with heritable pulmonary arterial hypertension (HPAH). However, only 30% of BMPR2 mutation carriers develop PAH, and we cannot predict which of these carriers will develop clinical disease. One possibility is that the nature of the BMPR2 mutation affects disease severity. This hypothesis has been difficult to test clinically, given the rarity of HPAH and the complexity of the confounding genetic and environmental risk factors...
December 2016: Pulmonary Circulation
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