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https://www.readbyqxmd.com/read/28088781/mir-30c-5p-ameliorates-hepatic-steatosis-in-leptin-receptor-deficient-db-db-mice-via-down-regulating-fasn
#1
Jiahui Fan, Huaping Li, Xiang Nie, Zhongwei Yin, Yanru Zhao, Chen Chen, Dao Wen Wang
Approximately 15-40% of the general adult population suffers from non-alcoholic fatty liver disease (NAFLD) worldwide. However, no drug is currently licensed for its treatment. In this study, we observed a significant reduction of miR-30c-5p in the liver of leptin receptor-deficient (db/db) mice. Remarkably, recombinant adeno-associated virus (rAAV)-mediated delivery of miR-30c-5p was sufficient to attenuate triglyceride accumulation and hepatic steatosis in db/db mice. Through computational prediction, KEGG analysis and Ago2 co-immunoprecipitation, we identified that miR-30c-5p directly targeted fatty acid synthase, a key enzyme in fatty acid biosynthesis...
January 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28087276/drosophila-argonaute2-turnover-is-regulated-by-the-ubiquitin-proteasome-pathway
#2
Madoka Chinen, Elissa P Lei
Argonaute (AGO) proteins play a central role in the RNA interference (RNAi) pathway, which is a cytoplasmic mechanism important for post-transcriptional regulation of gene expression. In Drosophila, AGO2 also functions in the nucleus to regulate chromatin insulator activity and transcription. Although there are a number of studies focused on AGO2 function, the regulation of AGO2 turnover is not well understood. We found that mutation of T1149 or R1158 in the conserved PIWI domain causes AGO2 protein instability, but only T1149 affects RNAi activity...
January 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28075055/argonaute-2-immunoprecipitation-revealed-lats1-as-a-novel-pro-apoptotic-target-of-mir-21-in-t-cells
#3
Nato Teteloshvili, Katarzyna Smigielska-Czepiel, Ye Yuan, Annika Seitz, Debora de Jong, Bea Rutgers, Pytrick Jellema, Roelof Jan van der Lei, Izabella Slezak-Prochazka, Elisabeth Brouwer, Annemieke M H Boots, Bart-Jan Kroesen, Anke van den Berg, Joost Kluiver
MicroRNA (miR)-21 is an important suppressor of T-cell apoptosis that is also overexpressed in many types of cancers. The exact mechanisms underlying the anti-apoptotic effects of miR-21 are not well understood. In this study, we used the Jurkat T-cell line as a model to identify apoptosis-associated miR-21 target genes. We showed that expression of miR-21 rapidly increases upon αCD3/αCD28 activation of Jurkat cells. Inhibition of miR-21 reduced cell growth which could be explained by an increase in apoptosis...
January 11, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28053119/short-intron-derived-ncrnas
#4
Florent Hubé, Damien Ulveling, Alain Sureau, Sabrina Forveille, Claire Francastel
Introns represent almost half of the human genome, although they are eliminated from transcripts through RNA splicing. Yet, different classes of non-canonical miRNAs have been proposed to originate directly from intron splicing. Here, we considered the alternative splicing of introns as an interesting source of miRNAs, compatible with a developmental switch. We report computational prediction of new Short Intron-Derived ncRNAs (SID), defined as precursors of smaller ncRNAs like miRNAs and snoRNAs produced directly by splicing, and tested their dependence on each key factor in canonical or alternative miRNAs biogenesis (Drosha, DGCR8, DBR1, snRNP70, U2AF65, PRP8, Dicer, Ago2)...
January 3, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28030800/the-role-of-mir-17-92-in-the-miregulatory-landscape-of-ewing-sarcoma
#5
Raphaela Schwentner, David Herrero-Martin, Maximilian O Kauer, Cornelia N Mutz, Anna M Katschnig, Grzegorz Sienski, Javier Alonso, Dave Nt Aryee, Heinrich Kovar
MicroRNAs serve to fine-tune gene expression and play an important regulatory role in tissue specific gene networks. The identification and validation of miRNA target genes in a tissue still poses a significant problem since the presence of a seed sequence in the 3'UTR of an mRNA and its expression modulation upon ectopic expression of the miRNA do not reliably predict regulation under physiological conditions. The chimeric oncoprotein EWS-FLI1 is the driving pathogenic force in Ewing sarcoma. MiR-17-92, one of the most potent oncogenic miRNAs, was recently reported to be among the top EWS-FLI1 activated miRNAs...
December 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/28008821/cooperative-enhancement-of-translation-by-two-adjacent-microrna-122-argonaute-2-complexes-binding-to-the-5%C3%A2-untranslated-region-of-hepatitis-c-virus-rna
#6
Anika Nieder-Röhrmann, Nadia Dünnes, Gesche K Gerresheim, Lyudmila A Shalamova, Andreas Herchenröther, Michael Niepmann
The liver-specific microRNA-122 (miR-122) binds to two conserved binding sites in the 5´-untranslated region (5´UTR) of Hepatitis C Virus (HCV) RNA. This binding was reported to enhance HCV RNA replication, translation and stability. We have analyzed binding of miR-122/Argonaute 2 (Ago2) complexes to these sites using anti-Ago2-co-immunoprecipitation of radioactively labeled HCV RNAs along with ectopic miR-122 in HeLa cells. Our results show that the miR-122 target sites can be addressed separately. When both target sites were addressed simultaneously, we observed a synergistic binding of both miR/Ago2 complexes...
December 23, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/28003477/argonaute-proteins-regulate-hiv-1-multiply-spliced-rna-and-viral-production-in-a-dicer-independent-manner
#7
Agathe Eckenfelder, Emmanuel Ségéral, Natalia Pinzón, Damien Ulveling, Céline Amadori, Marine Charpentier, Sabine Nidelet, Jean-Paul Concordet, Jean-François Zagury, Jean-Christophe Paillart, Clarisse Berlioz-Torrent, Hervé Seitz, Stéphane Emiliani, Sarah Gallois-Montbrun
Argonaute (Ago) proteins associate with microRNAs (miRNAs) to form the core of the RNA-induced silencing complex (RISC) that mediates post-transcriptional gene silencing of target mRNAs. As key players in anti-viral defense, Ago proteins are thought to have the ability to interact with human immunodeficiency virus type 1 (HIV-1) RNA. However, the role of this interaction in regulating HIV-1 replication has been debated. Here, we used high throughput sequencing of RNA isolated by cross-linking immunoprecipitation (HITS-CLIP) to explore the interaction between Ago2 and HIV-1 RNA in infected cells...
December 20, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27928938/sequence-and-structure-based-analysis-of-proteins-involved-in-mirna-biogenesis
#8
Chhaya Sharma, Debasisa Mohanty
miRNA biogenesis is a multistage process for generation of a mature miRNA and involves several different proteins. In this work, we have carried out sequence as well as structure based analysis for crucial proteins involved in miRNA biogenesis, namely, Dicer, Drosha, Argonaute (Ago) and Exportin-5 to understand evolution of these proteins in animal kingdom and also to identify key sequence and structural features which are determinants of their function. Our analysis reveals that in animals the miRNA biogenesis pathway first originated in molluscs...
December 8, 2016: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/27928054/the-influence-of-the-5-terminal-nucleotide-on-agoshrna-activity-and-biogenesis-importance-of-the-polymerase-iii-transcription-initiation-site
#9
Elena Herrera-Carrillo, Zong-Liang Gao, Alex Harwig, Matthias T Heemskerk, Ben Berkhout
Recent evidence indicates that shRNAs with a relatively short basepaired stem do not require Dicer processing, but instead are processed by the Argonaute 2 protein (Ago2). We named these molecules AgoshRNAs as both their processing and silencing function are mediated by Ago2. This alternative processing yields only a single RNA guide strand, which can avoid off-target effects induced by the passenger strand of regular shRNAs. It is important to understand this alternative processing route in mechanistic detail such that one can design improved RNA reagents...
December 7, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27927008/microrna-296-5p-promotes-invasiveness-through-downregulation-of-nerve-growth-factor-receptor-and-caspase-8
#10
Hong Lee, Chang Hoon Shin, Hye Ree Kim, Kyung Hee Choi, Hyeon Ho Kim
Glioblastomas (GBM) are very difficult to treat and their aggressiveness is one of the main reasons for this as well as for the frequent recurrences. MicroRNAs posttranscriptionally regulate their target genes through interaction between their seed sequence and 3'UTR of the target mRNAs. We previously reported that miR-296-3p is regulated by neurofibromatosis 2 (NF2) and enhances the invasiveness of GBM cells via SOCS2/STAT3. In this study, we investigated whether miR-296-5p, which originates from the same precursor miRNA as miR-296-3p, can increase the invasiveness of GBM cells...
December 8, 2016: Molecules and Cells
https://www.readbyqxmd.com/read/27924488/elucidating-mechanisms-of-molecular-recognition-between-human-argonaute-and-mirna-using-computational-approaches
#11
Hanlun Jiang, Lizhe Zhu, Amélie Héliou, Xin Gao, Julie Bernauer, Xuhui Huang
MicroRNA (miRNA) and Argonaute (AGO) protein together form the RNA-induced silencing complex (RISC) that plays an essential role in the regulation of gene expression. Elucidating the underlying mechanism of AGO-miRNA recognition is thus of great importance not only for the in-depth understanding of miRNA function but also for inspiring new drugs targeting miRNAs. In this chapter we introduce a combined computational approach of molecular dynamics (MD) simulations, Markov state models (MSMs), and protein-RNA docking to investigate AGO-miRNA recognition...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924485/small-molecules-targeting-the-mirna-binding-domain-of-argonaute-2-from-computer-aided-molecular-design-to-rna-immunoprecipitation
#12
Teresa Bellissimo, Silvia Masciarelli, Elena Poser, Ilaria Genovese, Alberto Del Rio, Gianni Colotti, Francesco Fazi
The development of small-molecule-based target therapy design for human disease and cancer is object of growing attention. Recently, specific microRNA (miRNA) mimicking compounds able to bind the miRNA-binding domain of Argonaute 2 protein (AGO2) to inhibit miRNA loading and its functional activity were described. Computer-aided molecular design techniques and RNA immunoprecipitation represent suitable approaches to identify and experimentally determine if a compound is able to impair the loading of miRNAs on AGO2 protein...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27918527/induction-and-suppression-of-antiviral-rna-interference-by-influenza-a-virus-in-mammalian-cells
#13
Yang Li, Megha Basavappa, Jinfeng Lu, Shuwei Dong, D Alexander Cronkite, John T Prior, Hans-Christian Reinecker, Paul Hertzog, Yanhong Han, Wan-Xiang Li, Sihem Cheloufi, Fedor V Karginov, Shou-Wei Ding, Kate L Jeffrey
Influenza A virus (IAV) causes annual epidemics and occasional pandemics, and is one of the best-characterized human RNA viral pathogens(1). However, a physiologically relevant role for the RNA interference (RNAi) suppressor activity of the IAV non-structural protein 1 (NS1), reported over a decade ago(2), remains unknown(3). Plant and insect viruses have evolved diverse virulence proteins to suppress RNAi as their hosts produce virus-derived small interfering RNAs (siRNAs) that direct specific antiviral defence(4-7) by an RNAi mechanism dependent on the slicing activity of Argonaute proteins (AGOs)(8,9)...
December 5, 2016: Nature Microbiology
https://www.readbyqxmd.com/read/27903911/mirtar2go-a-novel-rule-based-model-learning-method-for-cell-line-specific-microrna-target-prediction-that-integrates-ago2-clip-seq-and-validated-microrna-target-interaction-data
#14
Alireza Ahadi, Gaurav Sablok, Gyorgy Hutvagner
MicroRNAs (miRNAs) are ∼19-22 nucleotides (nt) long regulatory RNAs that regulate gene expression by recognizing and binding to complementary sequences on mRNAs. The key step in revealing the function of a miRNA, is the identification of miRNA target genes. Recent biochemical advances including PAR-CLIP and HITS-CLIP allow for improved miRNA target predictions and are widely used to validate miRNA targets. Here, we present miRTar2GO, which is a model, trained on the common rules of miRNA-target interactions, Argonaute (Ago) CLIP-Seq data and experimentally validated miRNA target interactions...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27895152/spatio-temporal-uncoupling-of-mirna-mediated-translational-repression-and-target-rna-degradation-controls-mirnp-recycling-in-mammalian-cells
#15
Mainak Bose, Bahnisikha Barman, Avijit Goswami, Suvendra N Bhattacharyya
miRNA-mediated repression control expression of more than half of protein coding genes in metazoan animals. Translation repression is associated with target mRNA degradation initiated by decapping and deadenylation of the repressed mRNAs. Earlier evidence suggest Endoplasmic Reticulum (ER) as the site where miRNPs interact with their targets before the translation repression sets in but the subcellular location of subsequent degradation of miRNA-repressed messages is largely unidentified. Here, we explore the subcellular distribution of essential components of degradation machineries of miRNA-targeted mRNAs...
November 28, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27867378/improved-pathogenicity-of-a-beet-black-scorch-virus-variant-by-low-temperature-and-co-infection-with-its-satellite-rna
#16
Jin Xu, Deshui Liu, Yongliang Zhang, Ying Wang, Chenggui Han, Dawei Li, Jia-Lin Yu, Xian-Bing Wang
Co-infection of none-coding satellite RNAs (sat-RNAs) usually inhibits replication and attenuates disease symptoms of helper viruses. However, we find that the sat-RNA of Beet black scorch virus (BBSV) and low temperature (18°C) additively enhance the systemic infection of BBSV in Nicotiana benthamiana. Northern blotting hybridization revealed a relatively reduced accumulation of BBSV-derived small interfering RNAs (siRNAs) in presence of sat-RNA as compared to that of BBSV alone. Cloning and sequencing of total small RNAs showed that more than 50% of the total small RNAs sequenced from BBSV-infected plants were BBSV-siRNAs, whereas the abundance of sat-siRNAs were higher than BBSV-siRNAs in the sat-RNA co-infected plants, indicating that the sat-RNA occupies most of the silencing components and possibly relieves the RNA silencing-mediated defense against BBSV...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27829158/amygdalar-microrna-15a-is-essential-for-coping-with-chronic-stress
#17
Naama Volk, Julius C Pape, Mareen Engel, Anthony S Zannas, Nadia Cattane, Annamaria Cattaneo, Elisabeth B Binder, Alon Chen
MicroRNAs are important regulators of gene expression and associated with stress-related psychiatric disorders. Here, we report that exposing mice to chronic stress led to a specific increase in microRNA-15a levels in the amygdala-Ago2 complex and a concomitant reduction in the levels of its predicted target, FKBP51, which is implicated in stress-related psychiatric disorders. Reciprocally, mice expressing reduced levels of amygdalar microRNA-15a following exposure to chronic stress exhibited increased anxiety-like behaviors...
November 8, 2016: Cell Reports
https://www.readbyqxmd.com/read/27770369/increasing-a-stable-transformation-efficiency-of-arabidopsis-by-manipulating-the-endogenous-gene-expression-using-virus-induced-gene-silencing
#18
Andriy Bilichak, Igor Kovalchuk
Virus-induced gene silencing (VIGS) is a powerful epigenetic tool that allows in a relatively short period of time to down-regulate the expression of an endogenous gene in infected plants for either monitoring the resulting phenotype or enhancing/modifying a particular trait associated with the gene. Here, we describe the utilization of Tobacco rattle virus (TRV) as a vector for the VIGS technique in Arabidopsis plants. The unique ability of TRV to infect both somatic tissues and gametes allows deciphering the role of genes in these tissues simultaneously...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27769040/microrna-like-viral-small-rna-from-porcine-reproductive-and-respiratory-syndrome-virus-negatively-regulates-viral-replication-by-targeting-the-viral-nonstructural-protein-2
#19
Na Li, Yunhuan Yan, Angke Zhang, Jiming Gao, Chong Zhang, Xue Wang, Gaopeng Hou, Gaiping Zhang, Jinbu Jia, En-Min Zhou, Shuqi Xiao
Many viruses encode microRNAs (miRNAs) that are small non-coding single-stranded RNAs which play critical roles in virus-host interactions. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically impactful viruses in the swine industry. The present study sought to determine whether PRRSV encodes miRNAs that could regulate PRRSV replication. Four viral small RNAs (vsRNAs) were mapped to the stem-loop structures in the ORF1a, ORF1b and GP2a regions of the PRRSV genome by bioinformatics prediction and experimental verification...
October 17, 2016: Oncotarget
https://www.readbyqxmd.com/read/27762650/antiviral-defense-involves-ago4-in-an-arabidopsis-potexvirus-interaction
#20
Chantal Brosseau, Mohamed El Oirdi, Ayooluwa Adurogbangba, Xiaofang Ma, Peter Moffett
In plants, RNA silencing regulates gene expression through the action of Dicer-like (DCL) and Argonaute (AGO) proteins via micro RNAs and RNA-dependent DNA methylation (RdDM). In addition, RNA silencing functions as an antiviral defense mechanism by targeting virus-derived double-stranded RNA. Plants encode multiple AGO proteins with specialized functions, including AGO4-like proteins that affect RdDM and AGO2, AGO5, and AGO1, which have antiviral activities. Here, we show that AGO4 is also required for defense against the potexvirus Plantago asiatica mosaic virus (PlAMV), most likely independent of RdDM components such as DCL3, Pol IV, and Pol V...
November 2016: Molecular Plant-microbe Interactions: MPMI
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