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Rna induced silencing complex

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https://www.readbyqxmd.com/read/28791440/therapeutic-potentials-of-short-interfering-rnas
#1
REVIEW
Chit Tam, Jack Ho Wong, Randy Chi Fai Cheung, Tao Zuo, Tzi Bun Ng
Short interfering RNA (siRNA) is one of the members of the family of RNA interference (RNAi). Coupled with the RNA-induced silencing complex (RISC), siRNA is able to trigger the cleavage of target RNAs which serve as a defensive system against pathogens. Meanwhile, siRNA in gene silencing opens a new avenue for the treatment of various diseases. SiRNA can effectively inhibit viral infection and replication and suppress tumorigenesis and various inflammation-associated diseases and cardiovascular diseases by inactivation of viral genes and downregulation of oncogene expression...
August 8, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28768867/mechanism-of-interferon-stimulated-gene-induction-in-hiv-1-infected-macrophages
#2
Najla Nasr, Abdullateef A Alshehri, Thomas K Wright, Maryam Shahid, Bonnie M Heiner, Andrew N Harman, Rachel A Botting, Karla J Helbig, Michael R Beard, Kazuo Suzuki, Anthony D Kelleher, Paul Hertzog, Anthony L Cunningham
Viruses manipulate the complex interferon and interferon stimulated gene (ISG) system in different ways. We have previously shown that HIV inhibits type I and III interferons in its key target cells but directly stimulates a subset of >20 ISGs in macrophages and dendritic cells many of which are antiviral. Here we examined the mechanism of induction of ISGs and showed this occurred in two phases. The first phase was transient (0-24hpi) induced mainly by extracellular vesicles, and one of its component proteins HSP90α, contained within the HIV inoculum...
August 2, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28755203/micrornas-recruit-eif4e2-to-repress-translation-of-target-mrnas
#3
Shaohong Chen, Guangxia Gao
MicroRNAs (miRNAs) recruit the RNA-induced silencing complex (RISC) to repress the translation of target mRNAs. While the 5' 7-methylguanosine cap of target mRNAs has been well known to be important for miRNA repression, the underlying mechanism is not clear. Here we show that TNRC6A interacts with eIF4E2, a homologue of eIF4E that can bind to the cap but cannot interact with eIF4G to initiate translation, to inhibit the translation of target mRNAs. Downregulation of eIF4E2 relieved miRNA repression of reporter expression...
July 28, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28737923/cosilencing-intestinal-transglutaminase-2-and-interleukin-15-using-gelatin-based-nanoparticles-in-an-in-vitro-model-of-celiac-disease
#4
Husain Attarwala, Valerie Clausen, Prasoon Chaturvedi, Mansoor M Amiji
In this study, we have developed a type B gelatin nanoparticle based siRNA delivery system for silencing of intestinal transglutaminase-2 (TG2) and interleukin-15 (IL-15) genes in cultured human intestinal epithelial cells (Caco-2) and murine alveolar macrophage cells (J774A.1). Small interfering RNA (siRNA) targeting the TG2 or IL-15 gene was encapsulated within gelatin nanoparticles using ethanol-water solvent displacement method. Size, charge, and morphology of gelatin nanoparticles were evaluated using a Zetasizer instrument and transmission electron microscopy...
August 10, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28730528/sulforaphane-promotes-mitochondrial-protection-in-sh-sy5y-cells-exposed-to-hydrogen-peroxide-by-an-nrf2-dependent-mechanism
#5
Marcos Roberto de Oliveira, Flávia de Bittencourt Brasil, Cristina Ribas Fürstenau
Sulforaphane (SFN; C6H11NOS2) is an isothiocyanate found in cruciferous vegetables, such as broccoli, kale, and radish. SFN exhibits antioxidant, anti-apoptotic, anti-tumor, and anti-inflammatory activities in different cell types. However, it was not previously demonstrated whether and how this natural compound would exert mitochondrial protection experimentally. Therefore, we investigated here the effects of a pretreatment (for 30 min) with SFN at 5 μM on mitochondria obtained from human neuroblastoma SH-SY5Y cells exposed to hydrogen peroxide (H2O2) at 300 μM for 24 h...
July 20, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28728908/the-proteasome-maturation-protein-pomp-increases-proteasome-assembly-and-activity-in-psoriatic-lesional-skin
#6
Barbara A Zieba, Laurent Henry, Matthieu Lacroix, Mohamed Jemaà, Thierry Lavabre-Bertrand, Laurent Meunier, Olivier Coux, Pierre-Emmanuel Stoebner
BACKGROUND: The ubiquitin proteasome pathway is involved in the pathogenesis of psoriasis and proteasome subunits are increased in lesional psoriatic skin. Recent works have highlighted that proteasome levels can be regulated through modulation of proteasome assembly notably by the proteasome maturation protein POMP. OBJECTIVES: To investigate whether proteasome assembly and POMP expression are modified in psoriatic skin. METHODS: Proteasome assembly as well as expression of proteasome regulators were assessed in non-lesional and lesional psoriatic skin using native gel electrophoresis and western blots respectively...
April 30, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28727810/cucumber-mosaic-virus-coat-protein-modulates-the-accumulation-of-2b-protein-and-antiviral-silencing-that-causes-symptom-recovery-in-planta
#7
Xiao-Peng Zhang, De-Shui Liu, Teng Yan, Xiao-Dong Fang, Kai Dong, Jin Xu, Ying Wang, Jia-Lin Yu, Xian-Bing Wang
Shoot apical meristems (SAM) are resistant to most plant viruses due to RNA silencing, which is restrained by viral suppressors of RNA silencing (VSRs) to facilitate transient viral invasion of the SAM. In many cases chronic symptoms and long-term virus recovery occur, but the underlying mechanisms are poorly understood. Here, we found that wild-type Cucumber mosaic virus (CMVWT) invaded the SAM transiently, but was subsequently eliminated from the meristems. Unexpectedly, a CMV mutant, designated CMVRA that harbors an alanine substitution in the N-terminal arginine-rich region of the coat protein (CP) persistently invaded the SAM and resulted in visible reductions in apical dominance...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28701303/endothelial-cell-shp-2-negatively-regulates-neutrophil-adhesion-and-promotes-transmigration-by-enhancing-icam-1-ve-cadherin-interaction
#8
Meiping Yan, Xinhua Zhang, Ao Chen, Wei Gu, Jie Liu, Xiaojiao Ren, Jianping Zhang, Xiaoxiong Wu, Aaron T Place, Richard D Minshall, Guoquan Liu
Intercellular adhesion molecule-1 (ICAM-1) mediates the firm adhesion of leukocytes to endothelial cells and initiates subsequent signaling that promotes their transendothelial migration (TEM). Vascular endothelial (VE)-cadherin plays a critical role in endothelial cell-cell adhesion, thereby controlling endothelial permeability and leukocyte transmigration. This study aimed to determine the molecular signaling events that originate from the ICAM-1-mediated firm adhesion of neutrophils that regulate VE-cadherin's role as a negative regulator of leukocyte transmigration...
July 12, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28690315/targeting-nucleolin-for-better-survival-in-diffuse-large-b-cell-lymphoma
#9
N Jain, H Zhu, T Khashab, Q Ye, B George, R Mathur, R K Singh, Z Berkova, J F Wise, F K Braun, X Wang, K Patel, Z Y Xu-Monette, J Courty, K H Young, L Sehgal, F Samaniego
Anthracyclines have been a cornerstone in the cure of diffuse large B-cell lymphoma (DLBCL) and other hematological cancers. The ability of anthracyclines to eliminate DLBCL depends on the presence of topoisomerase-II-alpha (TopIIA), a DNA repair enzyme complex. We identified nucleolin as a novel binding partner of TopIIA. Abrogation of nucleolin sensitized DLBCL cells to TopIIA targeting agents (doxorubicin/etoposide). Silencing nucleolin and challenging DLBCL cells with doxorubicin enhanced the phosphorylation of H2AX (γH2AX-marker of DNA damage) and allowed DNA fragmentation...
July 10, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28689066/roles-of-a-mitochondrial-accsco2-gene-from-apis-cerana-cerana-in-oxidative-stress-responses
#10
Haihong Jia, Manli Ma, Na Zhai, Zhenguo Liu, Hongfang Wang, Xingqi Guo, Baohua Xu
In eukaryotes, cytochrome c oxidase (COX) is a multimeric protein complex that is the last enzyme in the respiratory electron transport chain of mitochondria. Syntheses of cytochrome c oxidase (SCO) proteins are copper-donor chaperones involved in metalation of the CuA redox center of COX. However, its other precise actions are not yet understood. Here, we report the characterization of AccSCO2 from Apis cerana cerana (Acc). Our data showed that AccSCO2 expression was induced by cold (4°C), CdCl2, HgCl2, ultraviolet (UV) light, and H2O2 and was inhibited by different pesticide treatments...
July 2, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28665784/the-evidence-for-a-microrna-product-of-human-drosha-gene
#11
Peter Mechtler, Sydney Johnson, Hannah Slabodkin, Amir B Cohanim, Leonid Brodsky, Eugene S Kandel
MicroRNAs are short RNA molecules that regulate function and stability of a large subset of eukaryotic mRNAs. In the main pathway of microRNA biogenesis, a short "hairpin" is excised from a primary transcript by ribonuclease DROSHA, followed by additional nucleolytic processing by DICER and inclusion of the mature microRNA into the RNA-induced silencing complex. We report that a microRNA-like molecule is encoded by human DROSHA gene within a predicted stem-loop element of the respective transcript. This putative mature microRNA is complementary to DROSHA transcript variant 1 and can attenuate expression of the corresponding protein...
June 30, 2017: RNA Biology
https://www.readbyqxmd.com/read/28662698/mov10-suppresses-retroelements-and-regulates-neuronal-development-and-function-in-the-developing-brain
#12
Geena Skariah, Joseph Seimetz, Miles Norsworthy, Monica C Lannom, Phillip J Kenny, Mohamed Elrakhawy, Craig Forsthoefel, Jenny Drnevich, Auinash Kalsotra, Stephanie Ceman
BACKGROUND: Moloney leukemia virus 10 (Mov10) is an RNA helicase that mediates access of the RNA-induced silencing complex to messenger RNAs (mRNAs). Until now, its role as an RNA helicase and as a regulator of retrotransposons has been characterized exclusively in cell lines. We investigated the role of Mov10 in the mouse brain by examining its expression over development and attempting to create a Mov10 knockout mouse. Loss of both Mov10 copies led to early embryonic lethality. RESULTS: Mov10 was significantly elevated in postnatal murine brain, where it bound retroelement RNAs and mRNAs...
June 29, 2017: BMC Biology
https://www.readbyqxmd.com/read/28656064/epigenomic-and-functional-characterization-of-junctophilin-3-jph3-as-a-novel-tumor-suppressor-being-frequently-inactivated-by-promoter-cpg-methylation-in-digestive-cancers
#13
Xiaotong Hu, Yeye Kuang, Lili Li, Haimei Tang, Qinglan Shi, Xingsheng Shu, Yanjiao Zhang, Francis Kl Chan, Qian Tao, Chao He
Junctophilin (JPH) proteins stabilize junctional membrane complexes between plasma membrane and endoplasmic reticulum, also implicated in some human diseases. JPH3 mutations are linked to Huntington's disease-like 2 syndrome. Through epigenomic study of a colon cancer cell line pair (HCT116 and DKO), we identified JPH3 as a methylated novel tumor suppressor gene (TSG) candidate at 16q24. We further studied its epigenetic alterations and functions in digestive tumorigenesis. JPH3 expression at the RNA level was found to be frequently silenced or reduced in colorectal and gastric cancers due to its promoter CpG methylation, which is associated with tumor progression and poor survival of digestive cancer patients...
2017: Theranostics
https://www.readbyqxmd.com/read/28656062/c-myc-is-required-for-braf-v600e-induced-epigenetic-silencing-by-h3k27me3-in-tumorigenesis
#14
Yiping Qu, Qi Yang, Juan Liu, Bingyin Shi, Meiju Ji, Gang Li, Peng Hou
BRAF(V600E) mutation is frequently found in human cancers particularly thyroid cancer and melanoma, and is involved in the regulation of gene expression through activating MAPK/Erk signaling. Trimethylation of histone 3 lysine 27 (H3K27me3) is a critical epigenetic mark for the maintenance of gene silencing in tumorigenesis. However, molecular mechanism underlying the complex interplay between these two molecular events remains to be explored. In the present study, we conducted chromatin immunoprecipitation combined with next-generation sequencing (ChIP-Seq) and expression microarray analysis in NIH3T3 cells to explore the relationship between H3K27me3 and transcriptional regulation by BRAF(V600E) mutation...
2017: Theranostics
https://www.readbyqxmd.com/read/28639789/anti-inflammatory-effect-of-anti-tnf-%C3%AE-sirna-cationic-phosphorus-dendrimer-nanocomplexes-administered-intranasally-in-a-murine-acute-lung-injury-model
#15
Adam Bohr, Nicolas Tsapis, Ilaria Andreana, Anais Chamarat, Camilla Foged, Claudine Delomenie, Magali Noiray, Nabil El Brahmi, Jean-Pierre Majoral, Serge Mignani, Elias Fattal
Inflammation is an essential component of many lung diseases, including asthma, chronic obstructive pulmonary disease (COPD), or acute lung injury. Our purpose was to design efficient carriers for lung delivery of small interfering RNA (siRNA) targeting tumor necrosis factor (TNF-α) in an acute lung injury model. To achieve this goal, two different types of phosphorus-based dendrimers with either pyrrolidinium or morpholinium as terminal protonated amino groups were selected for their better biocompatibility compared to other dendrimers...
July 5, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28634830/the-microrna-effector-rna-induced-silencing-complex-in-hidradenitis-suppurativa-a-significant-dysregulation-within-active-inflammatory-lesions
#16
S Hessam, M Sand, M Skrygan, Falk G Bechara
Recently, we could show that the expression levels of the key regulators of the microRNA (miRNA) maturation and transport were dysregulated in inflamed hidradenitis suppurativa (HS) tissue (Heyam et al. in Wiley Interdiscip Rev RNA 6:271-289, 2015). The RNA-induced silencing complex (RISC) is the central element of the miRNA pathway and regulates miRNA formation and function. We investigated the expression of the RISC components, namely transactivation-responsive RNA-binding protein-1 (TRBP1), TRBP2, protein activator (PACT) of the interferon-induced protein kinase R, Argonaute RISC Catalytic Component-1 (AGO1) and Component-2 (AGO2), metadherin, and staphylococcal nuclease and Tudor domain-containing-1 (SND1) in inflamed HS tissue compared to healthy and psoriatic controls by real-time reverse transcription polymerase chain reaction...
June 20, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28633325/malus-hupehensis-mir168-targets-to-argonaute1-and-contributes-to-the-resistance-against-botryosphaeria-dothidea-infection-by-altering-defense-responses
#17
Xinyi Yu, Yingjun Hou, Weiping Chen, Sanhong Wang, Peihong Wang, Shenchun Qu
MicroRNA-mediated post transcriptional regulation plays a fundamental role in various plant physiological processes, including responses to pathogens. MicroRNA168 has been implicated as an essential factor of miRNA pathways by targeting ARGONAUTE1 (AGO1), the core component of the RNA-induced silencing complex (RISC). A fluctuation in AGO1 expression influences various plant-pathogen interactions, and the homeostasis of AGO1 and miR168 accumulation is maintained by a complicated feedback regulatory loop. In this study, the connection between miR168 and the resistance of M...
June 13, 2017: Plant & Cell Physiology
https://www.readbyqxmd.com/read/28621718/using-small-rna-seq-data-to-detect-sirna-duplexes-induced-by-plant-viruses
#18
Xiaoran Niu, Yu Sun, Ze Chen, Rugang Li, Chellappan Padmanabhan, Jishou Ruan, Jan F Kreuze, KaiShu Ling, ZhangJun Fei, Shan Gao
Small interfering RNA (siRNA) duplexes are short (usually 21 to 24 bp) double-stranded RNAs (dsRNAs) with several overhanging nucleotides at both 5'- and 3'-ends. It has been found that siRNA duplexes bind the RNA-induced silencing complex (RISC) and cleave the sense strands with endonucleases. In this study, for the first time, we detected siRNA duplexes induced by plant viruses on a large scale using next-generation sequencing (NGS) data. In addition, we used the detected 21 nucleotide (nt) siRNA duplexes with 2 nt overhangs to construct a dataset for future data mining...
June 16, 2017: Genes
https://www.readbyqxmd.com/read/28608334/in-vitro-analysis-of-argonaute-mediated-target-cleavage-and-translational-repression-in-plants
#19
Yukihide Tomari, Hiro-Oki Iwakawa
MicroRNAs (miRNAs) are endogenous small RNAs, which negatively regulate expression of complementary target genes at the post-transcriptional level. In plants, miRNAs are mainly loaded onto ARGONAUTE1 to form RNA-induced silencing complexes (RISCs), which mediate target mRNA cleavage as well as translational repression. The cell-free system derived from tobacco BY-2 protoplasts has become a powerful tool not only for the analysis of RISC assembly mechanism but also for mechanistic dissection of plant RISC functions...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28608333/in-vitro-formation-of-plant-rna-induced-silencing-complexes-using-an-extract-of-evacuolated-tobacco-protoplasts
#20
Taichiro Iki, Masayuki Ishikawa, Manabu Yoshikawa
Small RNA-mediated gene silencing is involved in a variety of biological processes among many eukaryotic organisms. The silencing effector, generally referred to as RNA-induced silencing complex (RISC), comprises an ARGONAUTE (AGO) protein and a small single-stranded guide RNA in its core. RISCs recognize target genes containing sequences complementary to the guide RNA and repress their expression transcriptionally or posttranscriptionally. In vitro systems that recapitulate RISC assembly are useful not only to decipher the molecular mechanisms underlying the assembly process itself but also to dissect the downstream silencing pathways mediated by RISCs...
2017: Methods in Molecular Biology
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