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Rna induced silencing complex

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https://www.readbyqxmd.com/read/28350964/promoting-vaginal-distribution-of-e7-and-mcl-1-sirna-silencing-nanoparticles-for-cervical-cancer-treatment
#1
Anna Lechanteur, Tania Furst, Brigitte Evrard, Philippe Delvenne, Geraldine Piel, Pascale Hubert
There is an urgent need to develop a less aggressive and more effective treatment against cervical lesions induced by different high-risk human papillomavirus (HR-HPV). We investigated the potential of a cocktail of small interfering RNA (siRNA) directed against the oncoprotein E6 (E6), the oncoprotein E7 (E7) and/or the anti-apoptotic protein MCL-1 (MCL-1). The combination of siRNA anti-E7 and anti-MCL-1 demonstrated high efficacy on multiple HPV16 and HPV18 cell lines and no effects on healthy keratinocytes...
March 28, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28334781/auf1-facilitates-microrna-mediated-gene-silencing
#2
Kyung-Won Min, Myung Hyun Jo, Soochul Shin, Sylvia Davila, Richard W Zealy, Soo Im Kang, Lawson T Lloyd, Sungchul Hohng, Je-Hyun Yoon
Eukaryotic mRNA decay is tightly modulated by RNA-binding proteins (RBPs) and microRNAs (miRNAs). RBP AU-binding factor 1 (AUF1) has four isoforms resulting from alternative splicing and is critical for miRNA-mediated gene silencing with a distinct preference of target miRNAs. Previously, we have shown that AUF1 facilitates miRNA loading to Argonaute 2 (AGO2), the catalytic component of the RNA-induced silencing complex. Here, we further demonstrate that depletion of AUF1 abolishes the global interaction of miRNAs and AGO2...
February 28, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28330734/enhanced-cellular-uptake-and-gene-silencing-activity-of-sirna-using-temperature-responsive-polymer-modified-liposome
#3
Jian Wang, Eri Ayano, Yoshie Maitani, Hideko Kanazawa
Short interfering RNA (siRNA) delivery systems using nanoparticle carriers have been limited by inefficient intracellular delivery. One drawback is the poor cellular uptake of siRNA/particle complexes through the plasma membrane and release of the nucleic acids into the cytosol. In this study, to develop the temperature-responsive liposome as a novel carrier for siRNA delivery, we prepared lipoplexes and assessed cellular uptake of siRNA and gene silencing activity of target genes, compared with those of a commercial transfection reagent, Lipofectamine RNAiMAX, and non-modified or PEGylated liposomes...
March 19, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28326190/malat1-regulates-myogenic-differentiation-and-muscle-regeneration-through-modulating-myod-transcriptional-activity
#4
Xiaona Chen, Liangqiang He, Yu Zhao, Yuying Li, Suyang Zhang, Kun Sun, Karl So, Fengyuan Chen, Liang Zhou, Leina Lu, Lijun Wang, Xihua Zhu, Xichen Bao, Miguel A Esteban, Shinichi Nakagawa, Kannanganattu V Prasanth, Zhenguo Wu, Hao Sun, Huating Wang
Malat1 is one of the most abundant long non-coding RNAs in various cell types; its exact cellular function is still a matter of intense investigation. In this study we characterized the function of Malat1 in skeletal muscle cells and muscle regeneration. Utilizing both in vitro and in vivo assays, we demonstrate that Malat1 has a role in regulating gene expression during myogenic differentiation of myoblast cells. Specifically, we found that knockdown of Malat1 accelerates the myogenic differentiation in cultured cells...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28319645/the-atypical-genesis-and-bioavailability-of-the-plant-based-small-rna-mir2911-bulking-up-while-breaking-down
#5
Jian Yang, Natee Kongchan, Cecilia Primo Planta, Joel R Neilson, Kendal D Hirschi
SCOPE: The uptake of dietary plant small RNAs (sRNAs) in consumers remains controversial, which is mainly due to low dietary content in combination with poor fractional absorption. MIR2911, among all the plant sRNAs including microRNAs, has been shown to be one of the most robustly absorbed sRNAs. Here we analyze the unusual abundance and unique genesis of MIR2911 during vegetable processing. METHODS AND RESULTS: Using qRT-PCR, the abundance of MIR2911 increased dramatically in macerated tissues while other microRNAs degraded...
March 20, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28315487/xpln-is-modulated-by-hdac-inhibitors-and-negatively-regulates-sparc-expression-by-targeting-mtorc2-in-human-lung-fibroblasts
#6
Koichiro Kamio, Arata Azuma, Jiro Usuki, Kuniko Matsuda, Minoru Inomata, Nobuhiko Nishijima, Shioto Itakura, Hiroki Hayashi, Takeru Kashiwada, Nariaki Kokuho, Kenichiro Atsumi, Tomoyoshi Yamaguchi, Kazue Fujita, Yoshinobu Saito, Shinji Abe, Kaoru Kubota, Akihiko Gemma
Pathogenesis of idiopathic pulmonary fibrosis (IPF) remains unclear. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that participates in the assembly and turnover of the extracellular matrix, whose expression is regulated by transforming growth factor (TGF)-β1 through activation of mammalian target of rapamycin complex 2 (mTORC2). Exchange factor found in platelets, leukemic, and neuronal tissues (XPLN) is an endogenous inhibitor of mTORC2. However, whether XPLN modulates SPARC expression remains unknown...
March 14, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28304372/micrornas-mir-203-3p-mir-664-3p-and-mir-708-5p-are-associated-with-median-strain-lifespan-in-mice
#7
Benjamin P Lee, Ivana Burić, Anupriya George-Pandeth, Kevin Flurkey, David E Harrison, Rong Yuan, Luanne L Peters, George A Kuchel, David Melzer, Lorna W Harries
MicroRNAs (miRNAs) are small non-coding RNA species that have been shown to have roles in multiple processes that occur in higher eukaryotes. They act by binding to specific sequences in the 3' untranslated region of their target genes and causing the transcripts to be degraded by the RNA-induced silencing complex (RISC). MicroRNAs have previously been reported to demonstrate altered expression in several aging phenotypes such as cellular senescence and age itself. Here, we have measured the expression levels of 521 small regulatory microRNAs (miRNAs) in spleen tissue from young and old animals of 6 mouse strains with different median strain lifespans by quantitative real-time PCR...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28291845/human-suv3-helicase-regulates-growth-rate-of-the-hela-cells-and-can-localize-in-the-nucleoli
#8
Maciej Szewczyk, Natalia Fedoryszak-Kuśka, Katarzyna Tkaczuk, Jurek Dobrucki, Agnieszka Waligórska, Piotr P Stępień
The human SUV3 helicase (SUV3, hSUV3, SUPV3L1) is a DNA/RNA unwinding enzyme belonging to the class of DexH-box helicases. It localizes predominantly in the mitochondria, where it forms an RNA-degrading complex called mitochondrial degradosome with exonuclease PNP (polynucleotide phosphorylase). Association of this complex with the polyA polymerase can modulate mitochondrial polyA tails. Silencing of the SUV3 gene was shown to inhibit the cell cycle and to induce apoptosis in human cell lines. However, since small amounts of the SUV3 helicase were found in the cell nuclei, it was not clear whether the observed phenotypes of SUV3 depletion were of mitochondrial or nuclear origin...
2017: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/28291360/in-situ-gelling-liquid-crystalline-system-as-local-sirna-delivery-system
#9
Livia N Borgheti-Cardoso, Sander A A Kooijmans, Marcel H A M Fens, Roy van der Meel, Fabiana T M C Vicentini, Marcia C A Fantini, Maria Vitória L B Bentley, Raymond M Schiffelers
An effective short interfering RNA (siRNA) delivery system protects the siRNA from degradation, facilitates its cellular uptake, and promotes its release into the cytoplasm. Local administration of siRNA presents advantages over systemic administration, such as the possibility to use lower doses and allow local and sustained release. In this context, in situ solidifying organogels based on monoglycerides (MO), polyethylenimine (PEI), propylene glycol (PG) and tris buffer are an attractive strategy for intratumoral delivery of siRNA...
March 28, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28270624/abscisic-acid-induces-resistance-against-bamboo-mosaic-virus-through-argonaute-2-and-3
#10
Mazen Alazem, Meng-Hsun He, Peter Moffett, Na-Sheng Lin
Plant resistance to pathogens is tuned by defense-related hormones. Of which, ABA is well documented to moderate resistance against fungi and bacteria. However, ABA's contribution to resistance against viruses is pleiotropic. ABA affects callose deposition at plasmodesmata (therefore hindering the viral cell-to-cell movement), but here we show that when callose synthase is downregulated, ABA still induces resistance against Bamboo mosaic virus (BaMV) infection. By examining the potential connections between the ABA and RNA silencing pathway in Arabidopsis, we showed that ABA regulates the expression of almost the whole Argonaute (AGO) gene family, of which some are required for plant resistance against BaMV...
March 7, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28257521/exosome-secretion-affects-social-motility-in-trypanosoma-brucei
#11
Dror Eliaz, Sriram Kannan, Hadassa Shaked, Gil Arvatz, Itai Dov Tkacz, Lior Binder, Hiba Waldman Ben-Asher, Uthman Okalang, Vaibhav Chikne, Smadar Cohen-Chalamish, Shulamit Michaeli
Extracellular vesicles (EV) secreted by pathogens function in a variety of biological processes. Here, we demonstrate that in the protozoan parasite Trypanosoma brucei, exosome secretion is induced by stress that affects trans-splicing. Following perturbations in biogenesis of spliced leader RNA, which donates its spliced leader (SL) exon to all mRNAs, or after heat-shock, the SL RNA is exported to the cytoplasm and forms distinct granules, which are then secreted by exosomes. The exosomes are formed in multivesicular bodies (MVB) utilizing the endosomal sorting complexes required for transport (ESCRT), through a mechanism similar to microRNA secretion in mammalian cells...
March 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28246360/multiple-histone-lysine-methyltransferases-are-required-for-the-establishment-and-maintenance-of-hiv-1-latency
#12
Kien Nguyen, Biswajit Das, Curtis Dobrowolski, Jonathan Karn
We showed previously that the histone lysine methyltransferase (HKMT) H3K27me3 (EZH2) is the catalytic subunit of Polycomb repressive complex 2 (PRC2) and is required for the maintenance of HIV-1 latency in Jurkat T cells. Here we show, by using chromatin immunoprecipitation experiments, that both PRC2 and euchromatic histone-lysine N-methyltransferase 2 (EHMT2), the G9a H3K9me2-3 methyltransferase, are highly enriched at the proviral 5' long terminal repeat (LTR) and rapidly displaced upon proviral reactivation...
February 28, 2017: MBio
https://www.readbyqxmd.com/read/28230184/tobacco-vein-banding-mosaic-virus-6k2-protein-hijacks-nbpsbo1-for-virus-replication
#13
Chao Geng, Zhi-Yong Yan, De-Jie Cheng, Jin Liu, Yan-Ping Tian, Chang-Xiang Zhu, Hong-Yan Wang, Xiang-Dong Li
Chloroplast-bound vesicles are key components in viral replication complexes (VRCs) of potyviruses. The potyviral VRCs are induced by the second 6 kDa protein (6K2) and contain at least viral RNA and nuclear inclusion protein b. To date, no chloroplast protein has been identified to interact with 6K2 and involve in potyvirus replication. In this paper, we showed that the Photosystem II oxygen evolution complex protein of Nicotiana benthamiana (NbPsbO1) was a chloroplast protein interacting with 6K2 of Tobacco vein banding mosaic virus (TVBMV; genus Potyvirus) and present in the VRCs...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28228216/non-canonical-targets-play-an-important-role-in-mirna-stability-control-mechanism
#14
June Hyun Park, Chanseok Shin
MicroRNAs (miRNAs) regulate gene expression by guiding Argonaute (Ago) containing RNA-induced silencing complex (RISC) to specific target mRNA molecules. It is well established that miRNAs are stabilized by Ago proteins, but the molecular features that triggers miRNA destabilization from Ago proteins remain largely unknown. To explore the molecular mechanisms of how targets affect the stability of miRNAs in human Ago (hAgo) proteins, we employed an in vitro system that consists of a minimal hAgo2-RISC in HEK293T cell lysates...
February 23, 2017: BMB Reports
https://www.readbyqxmd.com/read/28223335/cooperation-of-musashi-2-numb-mdm2-and-p53-in-drug-resistance-and-malignant-biology-of-pancreatic-cancer
#15
Weiwei Sheng, Ming Dong, Chuanping Chen, Zixin Wang, Yunwei Li, Kewei Wang, Yuji Li, Jianping Zhou
Our earlier work showed that Musashi (MSI)-2 promoted the development of pancreatic cancer (PC) by down-regulating Numb, which prevented murine double-minute (MDM)-2-mediated p53 ubiquitin degradation. Thus, we investigate the relationship among MSI2, Numb, MDM2, and p53 in PC in vitro and invivo, an association that has not been reported to our knowledge. MSI2 had no relationship with mutant p53 (mtp53) and wild-type p53 (wtp53) in normal PC cells. However, in response to gemcitabine or cisplatin treatment, MSI2 silencing simultaneously down-regulated MDM2 and up-regulated Numb and wtp53 protein levels...
February 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28215221/targeting-chromatin-remodeling-in-inflammation-and-fibrosis
#16
J Yang, B Tian, A R Brasier
Mucosal surfaces of the human body are lined by a contiguous epithelial cell surface that forms a barrier to aerosolized pathogens. Specialized pattern recognition receptors detect the presence of viral pathogens and initiate protective host responses by triggering activation of the nuclear factor κB (NFκB)/RelA transcription factor and formation of a complex with the positive transcription elongation factor (P-TEFb)/cyclin-dependent kinase (CDK)9 and Bromodomain-containing protein 4 (BRD4) epigenetic reader...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28212430/a-calmodulin-like-protein-suppresses-rna-silencing-and-promotes-geminivirus-infection-by-degrading-sgs3-via-the-autophagy-pathway-in-nicotiana-benthamiana
#17
Fangfang Li, Nan Zhao, Zhenghe Li, Xiongbiao Xu, Yaqin Wang, Xiuling Yang, Shu-Sheng Liu, Aiming Wang, Xueping Zhou
A recently characterized calmodulin-like protein is an endogenous RNA silencing suppressor that suppresses sense-RNA induced post-transcriptional gene silencing (S-PTGS) and enhances virus infection, but the mechanism underlying calmodulin-like protein-mediated S-PTGS suppression is obscure. Here, we show that a calmodulin-like protein from Nicotiana benthamiana (NbCaM) interacts with Suppressor of Gene Silencing 3 (NbSGS3). Deletion analyses showed that domains essential for the interaction between NbSGS3 and NbCaM are also required for the subcellular localization of NbSGS3 and NbCaM suppressor activity...
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28204845/mirnas-target-databases-developmental-methods-and-target-identification-techniques-with-functional-annotations
#18
REVIEW
Nagendra Kumar Singh
PURPOSE: microRNA (miRNA) regulates diverse biological mechanisms and metabolisms in plants and animals. Thus, the discoveries of miRNA has revolutionized the life sciences and medical research.The miRNA represses and cleaves the targeted mRNA by binding perfect or near perfect or imperfect complementary base pairs by RNA-induced silencing complex (RISC) formation during biogenesis process. One miRNA interacts with one or more mRNA genes and vice versa, hence takes part in causing various diseases...
February 15, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28182006/coordinate-activities-of-brd4-and-cdk9-in-the-transcriptional-elongation-complex-are-required-for-tgf%C3%AE-induced-nox4-expression-and-myofibroblast-transdifferentiation
#19
Talha Ijaz, Mohammad Jamaluddin, Yingxin Zhao, Yueqing Zhang, Jayson Jay, Celeste C Finnerty, David N Herndon, Ronald G Tilton, Allan R Brasier
Transdifferentiation of quiescent dermal fibroblasts to secretory myofibroblasts has a central role in wound healing and pathological scar formation. This myofibroblast transdifferentiation process involves TGFβ-induced de novo synthesis of alpha smooth muscle cell actin (αSMA)+ fibers that enhance contractility as well as increased expression of extracellular matrix (ECM) proteins, including collagen and fibronectin. These processes are mediated upstream by the reactive oxygen species (ROS)-producing enzyme Nox4, whose induction by TGFβ is incompletely understood...
February 9, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28165654/identification-of-proteasomal-catalytic-subunit-psma6-as-a-therapeutic-target-for-lung-cancer
#20
Tomohiko Kakumu, Mitsuo Sato, Daiki Goto, Toshio Kato, Naoyuki Yogo, Tetsunari Hase, Masahiro Morise, Takayuki Fukui, Kohei Yokoi, Yoshitaka Sekido, Luc Girard, John D Minna, Lauren A Byers, John V Heymach, Kevin R Coombes, Masashi Kondo, Yoshinori Hasegawa
To identify potential therapeutic targets for lung cancer, we performed semi-genome-wide shRNA screening combined with the utilisation of genome-wide expression and copy number data. shRNA screening targeting 5,043 genes in NCI-H460 identified 51 genes as candidates. Pathway analysis revealed that the 51 genes were enriched for the five pathways, including ribosome, proteasome, RNA polymerase, pyrimidine metabolism and spliceosome pathways. We focused on the proteasome pathway that involved six candidate genes because its activation has been demonstrated in diverse human malignancies, including lung cancer...
February 6, 2017: Cancer Science
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