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https://www.readbyqxmd.com/read/29145464/cellular-hnrnp-a2-b1-interacts-with-the-np-of-influenza-a-virus-and-impacts-viral-replication
#1
Cheng-Kai Chang, Chi-Jene Chen, Chih-Ching Wu, Shiau-Wen Chen, Shin-Ru Shih, Rei-Lin Kuo
The viral ribonucleoprotein (vRNP) of influenza A virus is formed by virion RNA (vRNA), viral polymerase complex, and nucleoprotein (NP). The NP plays an important role in facilitating the replication and stabilization of viral RNA. To explore host factors that may be involved in the regulation of viral replication through interactions with NP, we conducted an immunoprecipitation experiment followed by mass spectrometry to identify NP-associated cellular proteins. Here, we demonstrate that NP can interact and colocalize with heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 in mammalian cells and that the interaction may occur via direct binding to the glycine-rich domain (GRD) of hnRNP A2/B1...
2017: PloS One
https://www.readbyqxmd.com/read/29133793/binding-to-smn2-pre-mrna-protein-complex-elicits-specificity-for-small-molecule-splicing-modifiers
#2
Manaswini Sivaramakrishnan, Kathleen D McCarthy, Sébastien Campagne, Sylwia Huber, Sonja Meier, Angélique Augustin, Tobias Heckel, Hélène Meistermann, Melanie N Hug, Pascale Birrer, Ahmed Moursy, Sarah Khawaja, Roland Schmucki, Nikos Berntenis, Nicolas Giroud, Sabrina Golling, Manuel Tzouros, Balazs Banfai, Gonzalo Duran-Pacheco, Jens Lamerz, Ying Hsiu Liu, Thomas Luebbers, Hasane Ratni, Martin Ebeling, Antoine Cléry, Sergey Paushkin, Adrian R Krainer, Frédéric H-T Allain, Friedrich Metzger
Small molecule splicing modifiers have been previously described that target the general splicing machinery and thus have low specificity for individual genes. Several potent molecules correcting the splicing deficit of the SMN2 (survival of motor neuron 2) gene have been identified and these molecules are moving towards a potential therapy for spinal muscular atrophy (SMA). Here by using a combination of RNA splicing, transcription, and protein chemistry techniques, we show that these molecules directly bind to two distinct sites of the SMN2 pre-mRNA, thereby stabilizing a yet unidentified ribonucleoprotein (RNP) complex that is critical to the specificity of these small molecules for SMN2 over other genes...
November 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/29127284/a-thermostable-cas9-with-increased-lifetime-in-human-plasma
#3
Lucas B Harrington, David Paez-Espino, Brett T Staahl, Janice S Chen, Enbo Ma, Nikos C Kyrpides, Jennifer A Doudna
CRISPR-Cas9 is a powerful technology that has enabled genome editing in a wide range of species. However, the currently developed Cas9 homologs all originate from mesophilic bacteria, making them susceptible to degradation and unsuitable for applications requiring cleavage at elevated temperatures. Here, we show that the Cas9 protein from the thermophilic bacterium Geobacillus stearothermophilus (GeoCas9) catalyzes RNA-guided DNA cleavage at elevated temperatures. GeoCas9 is active at temperatures up to 70 °C, compared to 45 °C for Streptococcus pyogenes Cas9 (SpyCas9), which expands the temperature range for CRISPR-Cas9 applications...
November 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/29124890/new-perspectives-on-telomerase-rna-structure-and-function
#4
REVIEW
Cherie Musgrove, Linnea I Jansson, Michael D Stone
Telomerase is an ancient ribonucleoprotein (RNP) that protects the ends of linear chromosomes from the loss of critical coding sequences through repetitive addition of short DNA sequences. These repeats comprise the telomere, which together with many accessory proteins, protect chromosomal ends from degradation and unwanted DNA repair. Telomerase is a unique reverse transcriptase (RT) that carries its own RNA to use as a template for repeat addition. Over decades of research, it has become clear that there are many diverse, crucial functions played by telomerase RNA beyond simply acting as a template...
November 9, 2017: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/29114029/rapid-selection-free-high-efficiency-genome-editing-in-protozoan-parasites-using-crispr-cas9-ribonucleoproteins
#5
Lia Carolina Soares Medeiros, Lilith South, Duo Peng, Juan M Bustamante, Wei Wang, Molly Bunkofske, Natasha Perumal, Fernando Sanchez-Valdez, Rick L Tarleton
Trypanosomatids (order Kinetoplastida), including the human pathogens Trypanosoma cruzi (agent of Chagas disease), Trypanosoma brucei, (African sleeping sickness), and Leishmania (leishmaniasis), affect millions of people and animals globally. T. cruzi is considered one of the least studied and most poorly understood tropical disease-causing parasites, in part because of the relative lack of facile genetic engineering tools. This situation has improved recently through the application of clustered regularly interspaced short palindromic repeats-CRISPR-associated protein 9 (CRISPR-Cas9) technology, but a number of limitations remain, including the toxicity of continuous Cas9 expression and the long drug marker selection times...
November 7, 2017: MBio
https://www.readbyqxmd.com/read/29101507/novel-synthesized-radical-containing-nanoparticles-limit-infarct-size-following-ischemia-and-reperfusion-in-canine-hearts
#6
Hiroshi Asanuma, Shoji Sanada, Toru Yoshitomi, Hideyuki Sasaki, Hiroyuki Takahama, Madoka Ihara, Hiroko Takahama, Yoshiro Shinozaki, Hidezo Mori, Masanori Asakura, Atsushi Nakano, Masaru Sugimachi, Yoshihiro Asano, Tetsuo Minamino, Seiji Takashima, Yukio Nagasaki, Masafumi Kitakaze
PURPOSE: Although nitroxyl radicals such as 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) scavenge free radicals, their short half-life and considerable side effects such as systemic hypotension and bradycardia have limited their clinical application. Since a radical-containing nanoparticle (RNP) delivers nitroxyl radicals with a prolonged half-life specific to ischemic hearts, we investigated whether RNPs reduce infarct size without the occurrence of substantial side effects and whether nitric oxide (NO) contributes to the cardioprotective effects of RNPs...
November 3, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/29096075/getting-mrna-containing-ribonucleoprotein-granules-out-of-a-nuclear-back-door
#7
REVIEW
Anup Parchure, Mary Munson, Vivian Budnik
A pivotal feature of long-lasting synaptic plasticity is the localization of RNAs and the protein synthesis machinery at synaptic sites. How and where ribonucleoprotein (RNP) transport granules that support this synthetic activity are formed is of fundamental importance. The prevailing model poses that the nuclear pore complex (NPC) is the sole gatekeeper for transit of cellular material in and out of the nucleus. However, insights from the nuclear assembly of large viral capsids highlight a back door route for nuclear escape, a process referred to nuclear envelope (NE) budding...
November 1, 2017: Neuron
https://www.readbyqxmd.com/read/29078371/numerous-interactions-act-redundantly-to-assemble-a-tunable-size-of-p-bodies-in-saccharomyces-cerevisiae
#8
Bhalchandra S Rao, Roy Parker
Eukaryotic cells contain multiple RNA-protein assemblies referred to as RNP granules, which are thought to form through multiple protein-protein interactions analogous to a liquid-liquid phase separation. One class of RNP granules consists of P bodies, which consist of nontranslating mRNAs and the general translation repression and mRNA degradation machinery. P bodies have been suggested to form predominantly through interactions of Edc3 and a prion-like domain on Lsm4. In this work, we provide evidence that P-body assembly can be driven by multiple different protein-protein and/or protein-RNA interactions, including interactions involving Dhh1, Psp2, and Pby1...
October 23, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29070793/cellular-splicing-factor-uap56-stimulates-trimeric-np-formation-for-assembly-of-functional-influenza-viral-ribonucleoprotein-complexes
#9
Yifan Hu, Vishal Gor, Kazuya Morikawa, Kyosuke Nagata, Atsushi Kawaguchi
The influenza virus RNA genome exists as a ribonucleoprotein (RNP) complex by interacting with NP, one of virus-encoded RNA binding proteins. It is proposed that trimeric NP is a functional form, but it is not clear how trimeric NP is formed and transferred to RNA. UAP56, a cellular splicing factor, functions as a molecular chaperone for NP and is required for the replication-coupled RNP formation of newly synthesized viral genome, but the details of NP transfer to viral RNA by UAP56 is unclear. Here we found that UAP56 is complexed with trimeric NP, but not monomeric NP...
October 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29062898/essential-assembly-factor-rpf2-forms-novel-interactions-within-the-5s-rnp-in-trypanosoma-brucei
#10
Anyango D Kamina, Daniel Jaremko, Linda Christen, Noreen Williams
Ribosome biogenesis is a highly complex and conserved cellular process that is responsible for making ribosomes. During this process, there are several assembly steps that function as regulators to ensure proper ribosome formation. One of these steps is the assembly of the 5S ribonucleoprotein particle (5S RNP) in the central protuberance of the 60S ribosomal subunit. In eukaryotes, the 5S RNP is composed of 5S rRNA, ribosomal proteins L5 and L11, and assembly factors Rpf2 and Rrs1. Our laboratory previously showed that in Trypanosoma brucei, the 5S RNP is composed of 5S rRNA, L5, and trypanosome-specific RNA binding proteins P34 and P37...
September 2017: MSphere
https://www.readbyqxmd.com/read/29038333/germ-granule-mediated-rna-regulation-in-male-germ-cells
#11
Tiina Lehtiniemi, Noora Kotaja
Germ cells have exceptionally diverse transcriptomes. Furthermore, the progress of spermatogenesis is accompanied by dramatic changes in gene expression patterns, the most drastic of them being near-to-complete transcriptional silencing during the final steps of differentiation. Therefore, accurate RNA regulatory mechanisms are critical for normal spermatogenesis. Cytoplasmic germ cell-specific ribonucleoprotein (RNP) granules, known as germ granules, participate in posttranscriptional regulation in developing male germ cells...
October 16, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/29035328/pterodontic-acid-isolated-from-laggera-pterodonta-inhibits-viral-replication-and-inflammation-induced-by-influenza-a-virus
#12
Wenda Guan, Jing Li, Qiaolian Chen, Zhihong Jiang, Rongping Zhang, Xinhua Wang, Zifeng Yang, Xiping Pan
Laggera pterodonta (DC.) Benth. is a traditional Chinese medicine. The previous study revealed that the crude extracts of this herb could inhibit influenza virus infection, but its anti-influenza components and underlying mechanism of action remain unknown. Column chromatography was performed to isolate components from the plant. Activity against influenza virus of the compound was determined by CPE inhibition assay. Neuraminidase (NA) inhibition was measured by chemiluminescence assay. The anti-virus and anti-inflammation effects were determined using dual-luciferase reporter assay, immunofluorescence, quantitative real-time PCR and luminex assay...
October 16, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29030843/cclip-seq-retrieval-of-chimeric-reads-from-hits-clip-clip-seq-libraries
#13
Panagiotis Alexiou, Manolis Maragkakis, Zissimos Mourelatos, Anastassios Vourekas
HITS-CLIP (High-Throughput Sequencing after in vivo Crosslinking and Immunoprecipitation, CLIP-Seq) libraries contain fragments of the RNA sequences bound in vivo by an RNA binding protein (RBP). Such fragments, especially if they represent RNA duplexes bound in vivo by the RBP, can occasionally be ligated together to form chimeric CLIP tags. Chimeric CLIP tags from Argonaute CLIP libraries can provide the exact base pairing profiles of small RNAs with their target RNA sequences, thus solving a critical problem in the field of post-transcriptional regulation...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29023197/mutational-landscape-of-rna-binding-proteins-in-human-cancers
#14
Yaseswini Neelamraju, Abel Gonzalez-Perez, Poornima Bhat-Nakshatri, Harikrishna Nakshatri, Sarath Chandra Janga
RNA Binding Proteins (RBPs) are a class of post-transcriptional regulatory molecules which are increasingly documented to be dysfunctional in cancer genomes. However, our current understanding of these alterations is limited. Here, we delineate the mutational landscape of ∼1300 RBPs in ∼6000 cancer genomes. Our analysis revealed that RBPs have an average of ∼3 mutations per Mb across 26 cancer types. We identified 281 RBPs to be enriched for mutations (GEMs) in at least one cancer type. GEM RBPs were found to undergo frequent frameshift and inframe deletions as well as missense, nonsense and silent mutations when compared to those that are not enriched for mutations...
October 12, 2017: RNA Biology
https://www.readbyqxmd.com/read/29017869/risk-assessment-and-quality-improvement-of-liquid-waste-management-in-taiwan-university-chemical-laboratories
#15
Chao-Chung Ho, Ming-Shu Chen
The policy of establishing new universities across Taiwan has led to an increase in the number of universities, and many schools have constructed new laboratories to meet students' academic needs. In recent years, there has been an increase in the number of laboratory accidents from the liquid waste in universities. Therefore, how to build a safety system for laboratory liquid waste disposal has become an important issue in the environmental protection, safety, and hygiene of all universities. This study identifies the risk factors of liquid waste disposal and presents an agenda for practices to laboratory managers...
October 7, 2017: Waste Management
https://www.readbyqxmd.com/read/28992255/plasma-membrane-associated-cation-binding-protein-1-like-protein-negatively-regulates-intercellular-movement-of-bamv
#16
Ying-Ping Huang, Ying-Wen Huang, I-Hsuan Chen, Lin-Ling Shenkwen, Yau-Huei Hsu, Ching-Hsiu Tsai
To establish a successful infection, a virus needs to replicate and move cell-to-cell efficiently. We investigated whether one of the genes upregulated in Nicotiana benthamiana after Bamboo mosaic virus (BaMV) inoculation was involved in regulating virus movement. We revealed the gene to be a plasma membrane-associated cation-binding protein 1-like protein, designated NbPCaP1L. The expression of NbPCaP1L in N. benthamiana was knocked down using Tobacco rattle virus-based gene silencing and consequently the accumulation of BaMV increased significantly to that of control plants...
October 13, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28991917/characterization-of-the-catalytic-center-of-the-ebola-virus-l-polymerase
#17
Marie Luisa Schmidt, Thomas Hoenen
BACKGROUND: Ebola virus (EBOV) causes a severe hemorrhagic fever in humans and non-human primates. While no licensed therapeutics are available, recently there has been tremendous progress in developing antivirals. Targeting the ribonucleoprotein complex (RNP) proteins, which facilitate genome replication and transcription, and particularly the polymerase L, is a promising antiviral approach since these processes are essential for the virus life cycle. However, until now little is known about L in terms of its structure and function, and in particular the catalytic center of the RNA-dependent RNA polymerase (RdRp) of L, which is one of the most promising molecular targets, has never been experimentally characterized...
October 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28979592/irreparable-radial-nerve-palsy-due-to-delayed-diagnostic-management-of-a-giant-lipoma-at-the-proximal-forearm-resulting-in-a-triple-tendon-transfer-procedure-case-report-and-brief-review-of-literature
#18
Ingo Schmidt
BACKGROUND: Non-traumatic radial nerve palsy (RNP) caused by local tumors is a rare and uncommon entity. METHODS: A 62-year-old female presented with a left non-traumatic RNP, initially starting with weakness only. It was caused by a benign giant lipoma at the proximal forearm that was misdiagnosed over a period of 2 years. The slowly growth of the tumor led to an irreparable overstretching-related partial nerve disruption. For functional recovery of the patient, a triple tendon transfer procedure had to be performed...
2017: Open Orthopaedics Journal
https://www.readbyqxmd.com/read/28974576/microrna-mir-128-represses-line-1-retrotransposition-by-downregulating-the-nuclear-import-factor-tnpo1
#19
Adam Idica, Evgueni A Sevrioukov, Dimitri G Zisoulis, Matthias Hamdorf, Iben Daugaard, Pavan Kadandale, Irene Munk Pedersen
Repetitive elements, including LINE-1 (L1), comprise approximately half of the human genome. These elements can potentially destabilize the genome by initiating their own replication and reintegration into new sites (retrotransposition). In somatic cells, transcription of L1 elements are repressed by distinct molecular mechanisms including DNA methylation and histone modifications to repress transcription. Under conditions of hypomethylation (e.g. in tumor cells) a window of opportunity for L1 de-repression arises and additional restriction mechanisms become crucial...
October 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28971852/chance-and-necessity-in-the-evolution-of-rnase-p
#20
Venkat Gopalan, Nayef Jarrous, Andrey S Krasilnikov
RNase P catalyzes 5-maturation of tRNAs in all three domains of life. This primary function is accomplished by either a ribozyme-centered ribonucleoprotein (RNP) or a protein-only variant (with one to three polypeptides). The large, multicomponent archaeal and eukaryotic RNase P RNPs appear disproportionate to the simplicity of their role in tRNA 5-maturation, prompting the question of why the seemingly gratuitously complex RNP forms of RNase P were not replaced with simpler protein counterparts. Here, motivated by growing evidence, we consider the hypothesis that the large RNase P RNP was retained as a direct consequence of multiple roles played by its components in processes that are not related to the canonical RNase P function...
September 29, 2017: RNA
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