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Rna induced silencing complex

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https://www.readbyqxmd.com/read/29764744/effective-gene-silencing-activity-of-prodrug-type-2-o-methyldithiomethyl-sirna-compared-with-non-prodrug-type-2-o-methyl-sirna
#1
Junsuke Hayashi, Misa Nishigaki, Yosuke Ochi, Shun-Ichi Wada, Fumito Wada, Osamu Nakagawa, Satoshi Obika, Mariko Harada-Shiba, Hidehito Urata
Small interfering RNAs (siRNAs) are an active agent to induce gene silencing and they have been studied for becoming a biological and therapeutic tool. Various 2'-O-modified RNAs have been extensively studied to improve the nuclease resistance. However, the 2'-O-modified siRNA activities were often decreased by modification, since the bulky 2'-O-modifications inhibit to form a RNA-induced silencing complex (RISC). We developed novel prodrug-type 2'-O-methyldithiomethyl (MDTM) siRNA, which is converted into natural siRNA in an intracellular reducing environment...
May 8, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29761302/cftr-prevents-neuronal-apoptosis-following-cerebral-ischemia-reperfusion-via-regulating-mitochondrial-oxidative-stress
#2
Ya-Ping Zhang, Yong Zhang, Zhi-Bin Xiao, Yan-Bo Zhang, Jing Zhang, Zhi-Qiang Li, Yao-Bin Zhu
The cystic fibrosis transmembrane conductance regulator (CFTR) is linked to cell apoptosis and abundantly expressed in brain tissue. Mitochondrial oxidative stress plays a key role in activating apoptotic pathway following cerebral ischemia reperfusion (IR) injury. Reduced glutathione (GSH) is exclusively synthesized in cytosol but distributed in mitochondria. In the present study, we investigated whether CFTR affected mitochondrial oxidative stress via regulating GSH and thereby protected neurons against apoptosis following cerebral IR...
May 14, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29740830/mesenchymal-cell-differentiation-and-diseases-involvement-of-translin-trax-complexes-and-associated-proteins
#3
REVIEW
Masataka Kasai, Reiko Ishida, Kazuhiko Nakahara, Ko Okumura, Katsunori Aoki
Translin and translin-associated factor X (translin/TRAX) proteins have been implicated in a variety of cellular activities central to nucleic acid metabolism. Accumulating evidence indicates that translin/TRAX complexes participate in processes ensuring the replication of DNA, as well as cell division. Significant progress has been made in understanding the roles of translin/TRAX complexes in RNA metabolism, such as through RNA-induced silencing complex activation or the microRNA depletion that occurs in Dicer deficiency...
May 8, 2018: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29726599/the-roles-of-extracellular-vesicle-micrornas-in-the-central-nervous-system
#4
REVIEW
Stephanie N Blandford, Dylan A Galloway, Craig S Moore
MicroRNAs (miRNAs) are small, highly conserved non-coding RNA molecules that post-transcriptionally regulate protein expression and most biological processes. Mature miRNAs are recruited to the RNA-induced silencing complex (RISC) and target mRNAs via complementary base-pairing, thus resulting in translational inhibition and/or transcript degradation. Here, we present evidence implicating miRNAs within extracellular vesicles (EVs), including microvesicles and exosomes, as mediators of central nervous system (CNS) development, homeostasis, and injury...
May 4, 2018: Glia
https://www.readbyqxmd.com/read/29716623/mir-221-stimulates-breast-cancer-cells-and-cancer-associated-fibroblasts-cafs-through-selective-interference-with-the-a20-c-rel-ctgf-signaling
#5
Maria Francesca Santolla, Rosamaria Lappano, Francesca Cirillo, Damiano Cosimo Rigiracciolo, Anna Sebastiani, Sergio Abonante, Pierfrancesco Tassone, Pierosandro Tagliaferri, Maria Teresa Di Martino, Marcello Maggiolini, Adele Vivacqua
BACKGROUND: MicroRNA (miRNAs) are non-coding small RNA molecules that regulate gene expression by inhibiting the translation of target mRNAs. Among several dysregulated miRNAs in human cancer, the up-regulation of miR-221 has been associated with development of a variety of hematologic and solid malignancies. In this study, we investigated the involvement of miR-221 in breast cancer. METHODS: TaqMan microRNA assay was used to detect the miR-221 levels in normal cells and in MDA-MB 231 and SkBr3 breast cancer cells as well as in main players of the tumor microenvironment, namely cancer-associated fibroblasts (CAFs)...
May 2, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29712715/nmdar-dependent-argonaute-2-phosphorylation-regulates-mirna-activity-and-dendritic-spine-plasticity
#6
Dipen Rajgor, Thomas M Sanderson, Mascia Amici, Graham L Collingridge, Jonathan G Hanley
MicroRNAs (miRNAs) repress translation of target mRNAs by associating with Argonaute (Ago) proteins to form the RNA-induced silencing complex (RISC), underpinning a powerful mechanism for fine-tuning protein expression. Specific miRNAs are required for NMDA receptor (NMDAR)-dependent synaptic plasticity by modulating the translation of proteins involved in dendritic spine morphogenesis or synaptic transmission. However, it is unknown how NMDAR stimulation stimulates RISC activity to rapidly repress translation of synaptic proteins...
April 30, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29687822/probing-the-nanoparticle-ago2-interaction-for-enhanced-gene-knockdown
#7
Sonal Deshpande, Neetu Singh
RNAi is emerging as a promising technology for treatment of various diseases due to its ability to silence specific target genes. To date, a number of nanoparticle based formulations have been reported for the delivery of small interfering RNA (siRNA), with continuous modifications in the nanoparticle design for enhancing their efficiency. While majority of the design aspects are focused on avoiding or overcoming endosomal entrapment, limited studies are available that address the role of interaction of nanoparticles with the RNA induced silencing complex (RISC) machinery, which is a crucial aspect deciding the outcome...
April 24, 2018: Soft Matter
https://www.readbyqxmd.com/read/29676248/rnase-e-and-the-high-fidelity-orchestration-of-rna-metabolism
#8
Katarzyna J Bandyra, Ben F Luisi
The bacterial endoribonuclease RNase E occupies a pivotal position in the control of gene expression, as its actions either commit transcripts to an irreversible fate of rapid destruction or unveil their hidden functions through specific processing. Moreover, the enzyme contributes to quality control of rRNAs. The activity of RNase E can be directed and modulated by signals provided through regulatory RNAs that guide the enzyme to specific transcripts that are to be silenced. Early in its evolutionary history, RNase E acquired a natively unfolded appendage that recruits accessory proteins and RNA...
April 2018: Microbiology Spectrum
https://www.readbyqxmd.com/read/29669595/imp1-regulates-uca1-mediated-cell-invasion-through-facilitating-uca1-decay-and-decreasing-the-sponge-effect-of-uca1-for-mir-122-5p
#9
Yanchun Zhou, Xiuhua Meng, Shaoying Chen, Wei Li, Delin Li, Robert Singer, Wei Gu
BACKGROUND: Long noncoding RNAs (LncRNAs) represent a class of widespread and diverse endogenous RNAs that can posttranscriptionally regulate gene expression through the interaction with RNA-binding proteins and micro RNAs (miRNAs). Here, we report that in breast carcinoma cells, the insulin-like growth factor 2 messenger RNA binding protein (IMP1) binds to lncRNA urethral carcinoma-associated 1 (UCA1) and suppresses the UCA1-induced invasive phenotype. METHODS: RT-qPCR and RNA sequence assays were used to investigate the expression of UCA1 and miRNAs in breast cancer cells in response to IMP1 expression...
April 18, 2018: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/29661849/feedback-regulation-by-antagonistic-epigenetic-factors-potentially-maintains-homeostasis-in-drosophila
#10
Devendran A Sadasivam, Der-Hwa Huang
Polycomb group (PcG) repressors confer epigenetically heritable silencing on key regulatory genes through histone H3 trimethylation on lysine 27 (H3K27me3). How the silencing state withstands antagonistic activities from co-expressed trithorax group (trxG) activators is unclear. Using overexpression of Trx H3K4 methylase to perturb the silenced state, we find a dynamic process triggered in a stepwise fashion to neutralize the inductive impacts from excess Trx. Shortly after Trx overexpression, there are global increases in H3K4 trimethylation and RNA polymerase II phosphorylation, marking active transcription...
April 16, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29620261/upregulation-of-e%C3%A2-cadherin-expression-mediated-by-a-novel-dsrna-suppresses-the-growth-and-metastasis-of-bladder-cancer-cells-by-inhibiting-%C3%AE-catenin-tcf-target-genes
#11
Chuanchang Li, Jiaxuan Liu, Qingsong Zhang, Kai Cui, Qiangqiang Ge, Chenghe Wang, Zhong Chen
Low expression levels of E‑cadherin are correlated with poor prognosis in patients with bladder cancer (BCa). A small activating RNA (saRNA) targeting a specific promoter region can activate gene expression. In the present study, two small double-stranded RNAs (dsRNAs) targeting the promoter region of human E‑cadherin were designed and synthesized, and the regulatory role of saRNAs in E‑cadherin expression was investigated. The results of reverse transcription-quantitative polymerase chain reaction and western blotting demonstrated that transfection of dsEcad‑346 into the BCa cell lines T24 and 5637 significantly activated E‑cadherin expression...
March 29, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29569051/induction-and-relocalization-of-telomeric-repeat-containing-rnas-during-diauxic-shift-in-budding-yeast
#12
Carmina Angelica Perez-Romero, Maxime Lalonde, Pascal Chartrand, Emilio Cusanelli
Telomeres are maintained in a heterochromatic state that represses transcription of subtelomeric genes, a phenomenon known as telomere position effect. Nevertheless, telomeric DNA is actively transcribed, leading to the synthesis of telomeric repeat-containing noncoding RNA or TERRA. This nuclear noncoding RNA has been proposed to play important roles at telomeres, regulating their silencing, capping, repair and elongation by telomerase. In the budding yeast Saccharomyces cerevisiae, TERRA accumulation is repressed by telomeric silencing and the Rat1 exonuclease...
March 22, 2018: Current Genetics
https://www.readbyqxmd.com/read/29563287/nonstructural-5a-impairs-dna-damage-repair-implication-of-hepatitis-c-virus-mediated-hepatocarcinogenesis
#13
Tram T Nguyen, Eun-Mee Park, Yun-Sook Lim, Soon B Hwang
RAD51-associated protein 1 (RAD51AP1) is a member of the multiprotein complexes postulated to carry out RAD51-mediated homologous recombination and DNA repair in mammalian cells. In the present study, we showed that hepatitis C virus (HCV) NS5A directly bound RAD51AP1 and increased protein level of RAD51AP1 through modulation of the ubiquitin-proteasome pathway. We also demonstrated that RAD51AP1 protein levels were increased in the liver tissues of HCV-infected patients and NS5A transgenic mice. Importantly, NS5A impaired DNA repair by disrupting RAD51/RAD51AP1/UAF1 complex and rendered HCV-infected cells more sensitive to DNA damage...
March 21, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29562354/viral-fitness-correlates-with-the-magnitude-and-direction-of-the-perturbation-induced-in-the-host-s-transcriptome-the-tobacco-etch-potyvirus-tobacco-case-study
#14
Héctor Cervera, Silvia Ambrós, Guillermo P Bernet, Guillermo Rodrigo, Santiago F Elena
Determining the fitness of viral genotypes has become a standard practice in virology as it is essential to evaluate their evolutionary potential. Darwinian fitness, defined as the advantage of a given genotype with respect to a reference, is a complex property that captures, in a single figure, differences in performance at every stage of viral infection. To what extent does viral fitness result from specific molecular interactions with host factors and regulatory networks during infection? Can we identify host genes in functional classes whose expression depends on viral fitness? Here, we compared the transcriptomes of tobacco plants infected with seven genotypes of tobacco etch potyvirus (TEV) that differ in fitness...
March 19, 2018: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/29554310/4ehp-independent-repression-of-endogenous-mrnas-by-the-rna-binding-protein-gigyf2
#15
Cinthia C Amaya Ramirez, Petra Hubbe, Nicolas Mandel, Julien Béthune
Initially identified as a factor involved in tyrosine kinase receptor signaling, Grb10-interacting GYF protein 2 (GIGYF2) has later been shown to interact with the 5' cap-binding protein 4EHP as part of a translation repression complex, and to mediate post-transcriptional repression of tethered reporter mRNAs. A current model proposes that GIGYF2 is indirectly recruited to mRNAs by specific RNA-binding proteins (RBPs) leading to translation repression through its association with 4EHP. Accordingly, we recently observed that GIGYF2 also interacts with the miRNA-induced silencing complex and probably modulates its translation repression activity...
March 15, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29540675/expression-of-lncrna-mir222hg-co-transcribed-from-the-mir-221-222-gene-promoter-facilitates-the-development-of-castration-resistant-prostate-cancer
#16
Tong Sun, Shin-Yi Du, Joshua Armenia, Fangfang Qu, Jingyu Fan, Xiaodong Wang, Teng Fei, Kazumasa Komura, Shirley X Liu, Gwo-Shu Mary Lee, Philip W Kantoff
Mechanisms by which non-coding RNAs contribute to the progression of hormone-sensitive prostate cancer (PCa) (HSPC) to castration-resistant PCa (CRPC) remain largely unknown. We previously showed that microRNA-221/222 is up-regulated in CRPC and plays a critical role in modulating androgen receptor function during CRPC development. With further investigation, we characterized a putative promoter region located 23.3 kb upstream of the miR-221/222 gene, and this promoter is differentially activated in CRPC LNCaP-Abl cells, leading to the up-regulation of miR-221/222...
March 13, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29540601/positive-regulation-of-hepatitis-e-virus-replication-by-microrna-122
#17
Bangari Haldipur, Prudhvi Lal Bhukya, Vidya Arankalle, Kavita Lole
The molecular mechanisms of liver pathology and clinical disease in hepatitis E virus (HEV) infection remain unclear. MicroRNAs (miRNAs) are known to modulate viral pathogenesis either by directly altering viral gene expression or by enhancing cellular antiviral responses. Given the importance of microRNA-122 (miR-122) in liver pathobiology, we investigated possible role of miR-122 in HEV infection. In silico predictions using HEV genotype 1 (HEV-1), HEV-2, HEV-3, and HEV-4 sequences showed that the majority of genomes (203/222) harbor at least one miR-122/microRNA-122-3p (miR-122*) target site...
June 1, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29519815/structural-and-functional-analyses-reveal-the-contributions-of-the-c-and-n-lobes-of-argonaute-protein-to-selectivity-of-rna-target-cleavage
#18
Daniel M Dayeh, Bradley C Kruithoff, Kotaro Nakanishi
Some gene transcripts have cellular functions as regulatory noncoding RNAs. For example, ∼23-nucleotide (nt)-long siRNAs are loaded into Argonaute proteins. The resultant ribonucleoprotein assembly, the RNA-induced silencing complex (RISC), cleaves RNAs that are extensively base-paired with the loaded siRNA. To date, base complementarity is recognized as the major determinant of specific target cleavage (or slicing), but little is known about how Argonaute inspects base pairing before cleavage. A hallmark of Argonaute proteins is their bilobal structure, but despite the significance of this structure for curtailing slicing activity against mismatched targets, the molecular mechanism remains elusive...
April 27, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29503647/the-host-restriction-factor-interferon-inducible-transmembrane-protein-3-inhibits-vaccinia-virus-infection
#19
Chang Li, Shouwen Du, Mingyao Tian, Yuhang Wang, Jieying Bai, Peng Tan, Wei Liu, Ronglan Yin, Maopeng Wang, Ying Jiang, Yi Li, Na Zhu, Yilong Zhu, Tiyuan Li, Shipin Wu, Ningyi Jin, Fuchu He
Interferons (IFNs) establish dynamic host defense mechanisms by inducing various IFN-stimulated genes that encodes many antiviral innate immune effectors. IFN-inducible transmembrane (IFITM) proteins have been identified as intrinsic antiviral effectors, which block the entry of a broad spectrum of enveloped RNA viruses by interrupting virus-endosomal fusion. However, antiviral activity of IFITM proteins against mammalian DNA virus has not been demonstrated till date. Here, we sought to investigate the antiviral activities and mechanisms of interferon-inducible transmembrane protein 3 (IFITM3) protein against poxvirus infection...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29499952/piwil1-pirna-dq593109-regulates-the-permeability-of-the-blood-tumor-barrier-via-the-meg3-mir-330-5p-runx3-axis
#20
Shuyuan Shen, Hai Yu, Xiaobai Liu, Yunhui Liu, Jian Zheng, Ping Wang, Wei Gong, Jiajia Chen, Lini Zhao, Yixue Xue
The blood-tumor barrier (BTB) restricts the efficient delivery of anti-glioma drugs to cranial glioma tissues. Increased BTB permeability may allow greater delivery of the therapeutic agents. Increasing evidence has revealed that PIWI proteins and PIWI-interacting RNAs (piRNAs) play an important role in tumor progression. However, whether PIWI proteins and piRNAs regulate BTB permeability remains unclear. In the present study, we demonstrated that the PIWIL1/piRNA-DQ593109 (piR-DQ593109) complex was the predominant regulator of BTB permeability...
March 2, 2018: Molecular Therapy. Nucleic Acids
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