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https://www.readbyqxmd.com/read/28737923/co-silencing-intestinal-transglutaminase-2-and-interleukin-15-using-gelatin-based-nanoparticles-in-an-in-vitro-model-of-celiac-disease
#1
Husain Attarwala, Valerie Clausen, Prasoon Chaturvedi, Mansoor M Amiji
In this study, we have developed type B gelatin-based 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 Zetasizer instrument and transmission electron microscopy...
July 24, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28736447/prokaryotic-argonaute-proteins-novel-genome-editing-tools
#2
REVIEW
Jorrit W Hegge, Daan C Swarts, John van der Oost
Argonaute proteins constitute a highly diverse family of nucleic acid-guided proteins. They were first discovered in eukaryotes as key proteins in RNA interference systems, but homologous prokaryotic Argonaute proteins (pAgos) have also been found in archaea and bacteria. In this Progress article, we focus on long pAgo variants, a class of pAgos that are involved in nucleic acid-guided host defence against invading nucleic acids, and discuss the potential of pAgos in genome editing.
July 24, 2017: Nature Reviews. Microbiology
https://www.readbyqxmd.com/read/28735896/argonaute-clip-defines-a-deregulated-mir-122-bound-transcriptome-that-correlates-with-patient-survival-in-human-liver-cancer
#3
Joseph M Luna, Juan M Barajas, Kun-Yu Teng, Hui-Lung Sun, Michael J Moore, Charles M Rice, Robert B Darnell, Kalpana Ghoshal
MicroRNA-122, an abundant and conserved liver-specific miRNA, regulates hepatic metabolism and functions as a tumor suppressor, yet systematic and direct biochemical elucidation of the miR-122 target network remains incomplete. To this end, we performed Argonaute crosslinking immunoprecipitation (Argonaute [Ago]-CLIP) sequencing in miR-122 knockout and control mouse livers, as well as in matched human hepatocellular carcinoma (HCC) and benign liver tissue to identify miRNA target sites transcriptome-wide in two species...
July 13, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28719649/differential-expression-of-small-rna-pathway-genes-associated-with-the-biomphalaria-glabrata-schistosoma-mansoni-interaction
#4
Fábio Ribeiro Queiroz, Luciana Maria Silva, Wander de Jesus Jeremias, Élio Hideo Babá, Roberta Lima Caldeira, Paulo Marcos Zech Coelho, Matheus de Souza Gomes
The World Health Organization (WHO) estimates that approximately 240 million people in 78 countries require treatment for schistosomiasis, an endemic disease caused by trematodes of the genus Schistosoma. In Brazil, Schistosoma mansoni is the only species representative of the genus whose passage through an invertebrate host, snails of the genus Biomphalaria, is obligatory before infecting a mammalian host, including humans. The availability of the genome and transcriptome of B. glabrata makes studying the regulation of gene expression, particularly the regulation of miRNA and piRNA processing pathway genes, possible...
2017: PloS One
https://www.readbyqxmd.com/read/28709769/exploring-the-mitochondrial-microrna-import-pathway-through-polynucleotide-phosphorylase-pnpase
#5
Danielle L Shepherd, Quincy A Hathaway, Mark V Pinti, Cody E Nichols, Andrya J Durr, Shruthi Sreekumar, Kristen M Hughes, Seth M Stine, Ivan Martinez, John M Hollander
Cardiovascular disease is the primary cause of mortality for individuals with type 2 diabetes mellitus. During the diabetic condition, cardiovascular dysfunction can be partially attributed to molecular changes in the tissue, including alterations in microRNA (miRNA) interactions. MiRNAs have been reported in the mitochondrion and their presence may influence cellular bioenergetics, creating decrements in functional capacity. In this study, we examined the roles of Argonaute 2 (Ago2), a protein associated with cytosolic and mitochondrial miRNAs, and Polynucleotide Phosphorylase (PNPase), a protein found in the inner membrane space of the mitochondrion, to determine their role in mitochondrial miRNA import...
July 11, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28709658/ngago-gdna-system-efficiently-suppresses-hepatitis-b-virus-replication-through-accelerating-decay-of-pregenomic-rna
#6
Zhuanchang Wu, Siyu Tan, Leiqi Xu, Lifen Gao, Haizhen Zhu, Chunhong Ma, Xiaohong Liang
Covalently closed circular DNA (cccDNA) in the hepatocytes nucleus is responsible for persistent infection of Hepatitis B virus (HBV). Current antiviral therapy drugs nucleos(t)ide analogs or interferon fail to eradicate HBV cccDNA. Genome editing technique provides an effective approach for HBV treatment through targeting viral cccDNA. Natronobacterium gregoryi Argonaute (NgAgo)-guide DNA (gDNA) system with powerful genome editing prompts us to explore its application in inhibiting HBV replication. Preliminary function verification indicated that NgAgo/EGFP-gDNA obviously inhibited EGFP expression...
July 12, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28708282/the-mechanism-of-long-non-coding-rna-meg3-for-hepatic-ischemia-reperfusion-mediated-by-mir-34a-nrf2-signaling-pathway
#7
Xinli Huang, Yun Gao, Jianjie Qin, Sen Lu
OBJECTIVE: To investigate the function of MEG3 in hepatic ischemia-reperfusion (HIR) progress, involving its association with the level of miR-34a during hypoxia-induced hypoxia re-oxygenation (H/R) in vitro. METHODS: HIR mice model in vivo was established.MEG3 , miR-34a expression, along with Nrf2 mRNA and protein level were detected in tissues and cells. Serum biochemical parameters (ALT and AST) were assessed in vivo. A potential binding region between MEG3 and miR34a was confirmed by luciferase assays...
July 14, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28698160/investigating-the-regulatory-roles-of-the-micrornas-and-the-argonaute-1-enriched-small-rnas-in-plant-metabolism
#8
Jingping Qin, Zhonghai Tang, Xiaoxia Ma, Yijun Meng
The biological roles of small RNAs (sRNAs) in metabolic processes are emerging. However, a systemic study is needed to investigate the wide-spread involvement of the sRNAs in plant metabolism. By using the metabolism-related transcripts retrieved from the public database Plant Metabolic Network, and the publicly available sRNA high-throughput sequencing data, large-scale target identification was performed for microRNAs (miRNAs) and Argonaute 1 (AGO1)-enriched sRNAs in Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa)...
July 8, 2017: Gene
https://www.readbyqxmd.com/read/28695996/downregulation-of-genes-coding-for-core-rnai-components-and-disease-resistance-proteins-via-corresponding-micrornas-might-be-correlated-with-successful-smv-infection-in-soybean
#9
Duran Bao, Oyunchuluun Ganbaatar, Xiuqi Cui, Ruonan Yu, Wenhua Bao, Bryce W Falk, Hada Wuriyanghan
Plants protect themselves from virus infections by several different defense mechanisms. RNA interference (RNAi) is one prominent antiviral mechanism, which requires the participation of AGO (Argonaute) and Dicer/DCL (Dicer-like) proteins. Effector-triggered immunity (ETI) is an antiviral mechanism mediated by resistance (R) genes, most of which encode NBS-LRR family proteins. MicroRNAs (miRNAs) play important regulatory roles in plants, including regulation of host defenses. SMV (Soybean mosaic virus) is the most common virus in soybean and here we identified dozens of SMV-responsive miRNAs by microarray analysis in a SMV-susceptible soybean line...
July 11, 2017: Molecular Plant Pathology
https://www.readbyqxmd.com/read/28683311/argonaute-utilization-for-mirna-silencing-is-determined-by-phosphorylation-dependent-recruitment-of-lim-domain-containing-proteins
#10
Katherine S Bridge, Kunal M Shah, Yigen Li, Daniel E Foxler, Sybil C K Wong, Duncan C Miller, Kathryn M Davidson, John G Foster, Ruth Rose, Michael R Hodgkinson, Paulo S Ribeiro, A Aziz Aboobaker, Kenta Yashiro, Xiaozhong Wang, Paul R Graves, Michael J Plevin, Dimitris Lagos, Tyson V Sharp
As core components of the microRNA-induced silencing complex (miRISC), Argonaute (AGO) proteins interact with TNRC6 proteins, recruiting other effectors of translational repression/mRNA destabilization. Here, we show that LIMD1 coordinates the assembly of an AGO-TNRC6 containing miRISC complex by binding both proteins simultaneously at distinct interfaces. Phosphorylation of AGO2 at Ser 387 by Akt3 induces LIMD1 binding, which in turn enables AGO2 to interact with TNRC6A and downstream effector DDX6. Conservation of this serine in AGO1 and 4 indicates this mechanism may be a fundamental requirement for AGO function and miRISC assembly...
July 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/28682306/unique-roles-for-histone-h3k9me-states-in-rnai-and-heritable-silencing-of-transcription
#11
Gloria Jih, Nahid Iglesias, Mark A Currie, Natarajan V Bhanu, Joao A Paulo, Steven P Gygi, Benjamin A Garcia, Danesh Moazed
Heterochromatic DNA domains play important roles in regulation of gene expression and maintenance of genome stability by silencing repetitive DNA elements and transposons. From fission yeast to mammals, heterochromatin assembly at DNA repeats involves the activity of small noncoding RNAs (sRNAs) associated with the RNA interference (RNAi) pathway(1-9). Typically, sRNAs, originating from long noncoding RNAs, guide Argonaute-containing effector complexes to complementary nascent RNAs to initiate histone H3 lysine 9 di- and tri-methylation (H3K9me2 and H3K9me3, respectively) and heterochromatin formation(10-17)...
June 22, 2017: Nature
https://www.readbyqxmd.com/read/28674805/a-recessive-genetic-screen-for-components-of-the-rna-interference-pathway-performed-in-mouse-embryonic-stem-cells
#12
Melanie I Trombly, Xiaozhong Wang
Several key components of the RNA interference (RNAi) pathway were identified in genetic screens performed in non-mammalian model organisms. To identify components of the mammalian RNAi pathway, we developed a recessive genetic screen in mouse embryonic stem (ES) cells. Recessive genetic screens are feasible in ES cells that are Bloom-syndrome protein deficient (Blm-deficient). We constructed a reporter cell line in Blm-deficient ES cells to isolate RNAi mutants using a simple drug selection scheme. This chapter describes how we used retroviral gene-traps to mutagenize the reporter cell line and select for RNAi mutants...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28674223/expression-analysis-of-argonaute-dicer-like-and-rna-dependent-rna-polymerase-genes-in-cucumber-cucumis-sativus-l-in-response-to-abiotic-stress
#13
Defang Gan, Mengdan Zhan, Feng Yang, Qiqi Zhang, Keling Hu, Wenjuan Xu, Qinghui Lu, Ling Zhang, Dandi Liang
Posttranscriptional control of gene expression can be achieved through RNA interference when the activities of Dicer-like (DCL), argonaute (AGO) and RNA-dependent RNA polymerase (RDR) proteins are significant. In this study, we analysed the expression of seven AGO, five DCL and eight RDR genes in cucumber under cold, heat, hormone, salinity and dehydration treatments using quantitative reverse-transcription PCR (qRT-PCR). All CsAGO, CsDCL and CsRDR genes were differentially expressed under abiotic stress treatment...
June 2017: Journal of Genetics
https://www.readbyqxmd.com/read/28673815/autoantibodies-to-su-argonaute-2-in-japanese-patients-with-inflammatory-myopathy
#14
Mariko Ogawa-Momohara, Yoshinao Muro, Minoru Satoh, Masashi Akiyama
BACKGROUND: Anti-Su antibodies are found in 5-20% of cases of various systemic autoimmune rheumatic diseases and in 5-10% of dermatomyositis (DM)/polymyositis (PM) patients. In 2006, the 100kDa Su antigen was identified as argonaute2 (Ago2), and it was found to play a major role in RNA interference. However, immunoprecipitation (IP) remains the main method for detecting anti-Su and the clinical significance of the antibodies is uncertain. METHODS: Sera from patients with DM/PM (n=224) were screened by an ELISA that uses recombinant biotinylated Ago2 protein...
June 30, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28663331/multiplexed-gene-editing-and-protein-over-expression-using-a-tobacco-mosaic-virus-viral-vector
#15
Will Cody, Herman B Scholthof, T Erik Mirkov
The CRISPR/Cas9 gene editing platform has been adapted as a transient screening device for most biological model systems, although a comparable transient system has yet to be regularly implemented in plant biology. Here, we use the Tobacco mosaic virus-derived viral vector, TRBO, to evaluate the ability of three single guide RNA (sgRNA) delivery constructs in Nicotiana benthamiana by measuring the presence of genomic indels (inserts and deletions) when co-delivered through agroinfiltration with a Cas9 nuclease expressing construct...
June 29, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28658626/functional-dissection-of-the-pol-v-largest-subunit-ctd-in-rna-directed-dna-methylation
#16
Jered M Wendte, Jeremy R Haag, Jasleen Singh, Anastasia McKinlay, Olga M Pontes, Craig S Pikaard
Plant multisubunit RNA polymerase V (Pol V) transcription recruits Argonaute-small interfering RNA (siRNA) complexes that specify sites of RNA-directed DNA methylation (RdDM) for gene silencing. Pol V's largest subunit, NRPE1, evolved from the largest subunit of Pol II but has a distinctive C-terminal domain (CTD). We show that the Pol V CTD is dispensable for catalytic activity in vitro yet essential in vivo. One CTD subdomain (DeCL) is required for Pol V function at virtually all loci. Other CTD subdomains have locus-specific effects...
June 27, 2017: Cell Reports
https://www.readbyqxmd.com/read/28657885/evolutionary-genomics-of-defense-systems-in-archaea-and-bacteria
#17
Eugene V Koonin, Kira S Makarova, Yuri I Wolf
Evolution of bacteria and archaea involves an incessant arms race against an enormous diversity of genetic parasites. Accordingly, a substantial fraction of the genes in most bacteria and archaea are dedicated to antiparasite defense. The functions of these defense systems follow several distinct strategies, including innate immunity, adaptive immunity, and dormancy induction, or programmed cell death. Recent comparative genomic studies taking advantage of the expanding database of microbial genomes and metagenomes, combined with direct experiments, resulted in the discovery of several previously unknown defense systems, including innate immunity centered on Argonaute proteins, bacteriophage exclusion, and new types of CRISPR-Cas systems of adaptive immunity...
June 28, 2017: Annual Review of Microbiology
https://www.readbyqxmd.com/read/28645918/phosphorylation-of-argonaute-proteins-affects-mrna-binding-and-is-essential-for-microrna-guided-gene-silencing-in%C3%A2-vivo
#18
Miguel Quévillon Huberdeau, Daniela M Zeitler, Judith Hauptmann, Astrid Bruckmann, Lucile Fressigné, Johannes Danner, Sandra Piquet, Nicholas Strieder, Julia C Engelmann, Guillaume Jannot, Rainer Deutzmann, Martin J Simard, Gunter Meister
Argonaute proteins associate with microRNAs and are key components of gene silencing pathways. With such a pivotal role, these proteins represent ideal targets for regulatory post-translational modifications. Using quantitative mass spectrometry, we find that a C-terminal serine/threonine cluster is phosphorylated at five different residues in human and Caenorhabditis elegans In human, hyper-phosphorylation does not affect microRNA binding, localization, or cleavage activity of Ago2. However, mRNA binding is strongly affected...
July 14, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28645154/alg-5-is-a-mirna-associated-argonaute-required-for-proper-developmental-timing-in-the-caenorhabditis-elegans-germline
#19
Kristen C Brown, Joshua M Svendsen, Rachel M Tucci, Brooke E Montgomery, Taiowa A Montgomery
Caenorhabditis elegans contains 25 Argonautes, of which, ALG-1 and ALG-2 are known to primarily interact with miRNAs. ALG-5 belongs to the AGO subfamily of Argonautes that includes ALG-1 and ALG-2, but its role in small RNA pathways is unknown. We analyzed by high-throughput sequencing the small RNAs associated with ALG-5, ALG-1 and ALG-2, as well as changes in mRNA expression in alg-5, alg-1 and alg-2 mutants. We show that ALG-5 defines a distinct branch of the miRNA pathway affecting the expression of genes involved in immunity, defense, and development...
June 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28642363/nuclear-phosphorylated-dicer-processes-double-stranded-rna-in-response-to-dna-damage
#20
Kaspar Burger, Margarita Schlackow, Martin Potts, Svenja Hester, Shabaz Mohammed, Monika Gullerova
The endoribonuclease Dicer is a key component of the human RNA interference pathway and is known for its role in cytoplasmic microRNA production. Recent findings suggest that noncanonical Dicer generates small noncoding RNA to mediate the DNA damage response (DDR). Here, we show that human Dicer is phosphorylated in the platform-Piwi/Argonaute/Zwille-connector helix cassette (S1016) upon induction of DNA damage. Phosphorylated Dicer (p-Dicer) accumulates in the nucleus and is recruited to DNA double-strand breaks...
June 22, 2017: Journal of Cell Biology
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