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https://www.readbyqxmd.com/read/28432338/crispr-cas9-mediated-inactivation-of-argonaute-2-reveals-its-differential-involvement-in-antiviral-responses
#1
Márta Ludman, József Burgyán, Károly Fátyol
RNA silencing constitutes an important antiviral mechanism in plants. Small RNA guided Argonaute proteins fulfill essential role in this process by acting as executors of viral restriction. Plants encode multiple Argonaute proteins of which several exhibit antiviral activities. A recent addition to this group is AGO2. Its involvement in antiviral responses is established predominantly by studies employing mutants of Arabidopsis thaliana. In the virological model plant, Nicotiana benthamiana, the contribution of AGO2 to antiviral immunity is much less certain due to the lack of appropriate genetic mutants...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28410363/highly-accessible-au-rich-regions-in-3-untranslated-regions-are-hotspots-for-binding-of-regulatory-factors
#2
Mireya Plass, Simon H Rasmussen, Anders Krogh
Post-transcriptional regulation is regarded as one of the major processes involved in the regulation of gene expression. It is mainly performed by RNA binding proteins and microRNAs, which target RNAs and typically affect their stability. Recent efforts from the scientific community have aimed at understanding post-transcriptional regulation at a global scale by using high-throughput sequencing techniques such as cross-linking and immunoprecipitation (CLIP), which facilitates identification of binding sites of these regulatory factors...
April 14, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28404816/pick1-ca-2-sensor-modulates-nmda-receptor-dependent-microrna-mediated-translational-repression-in-neurons
#3
Dipen Rajgor, Maria Fiuza, Gabrielle T Parkinson, Jonathan G Hanley
miRNAs are important regulators of localized mRNA translation in neuronal dendrites. The presence of RNA-induced silencing complex (RISC) proteins in these compartments and the dynamic miRNA expression changes that occur in response to neuronal stimulation highlights their importance in synaptic plasticity. Previously we demonstrated a novel interaction between the major RISC component Argounaute-2 (Ago2) and the BAR-domain protein PICK1. PICK1 recruits Ago2 to recycling endosomes in dendrites, where it inhibits miRNA-mediated translational repression...
April 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28388330/yellow-fever-virus-modulates-the-expression-of-key-proteins-related-to-the-microrna-pathway-in-the-human-hepatocarcinoma-cell-line-hepg2
#4
Gustavo Moraes Holanda, Samir Mansour Moraes Casseb, Karla Fabiane Lopes Mello, Pedro Fernando Costa Vasconcelos, Ana Cecília Ribeiro Cruz
Yellow fever is a zoonotic disease caused by the yellow fever virus (YFV) and transmitted by mosquitoes of the family Culicidae. It is well known that cellular and viral microRNAs (miRNAs) are involved in modulation of viral and cellular gene expression, as well as immune response, and are considered by the scientific community as possible targets for an effective therapy against viral infections. This regulation may be involved in different levels of infection and clinical symptomatology. We used viral titration techniques, viral kinetics from 24 to 96 hours postinfection (hpi), and analyzed the expression of key proteins related to the miRNA pathway by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR)...
April 7, 2017: Viral Immunology
https://www.readbyqxmd.com/read/28388001/exploring-the-rna-bound-and-rna-free-human-argonaute-2-by-molecular-dynamics-simulation-method
#5
Ren Kong, Lei Xu, Lianhua Piao, Dawei Zhang, Ting-Jun Hou, Shan Chang
Argonaute 2 (Ago2) protein is the major vehicle of MicroRNAs (miRNAs) guided gene repression and silencing processes. Although the crystal structure of human Ago2 (hAgo2) has recently been disclosed but the information of dynamically structural character of protein-RNA recognition is still lacking. Molecular dynamics simulations were used to systematically explore hAgo2 in the presence and absence of RNA duplex. Stable direct and water-mediated hydrogen bonds were observed between guide RNA backbone atoms and hAgo2, especially for nucleotides 2-7...
April 7, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28381573/potato-virus-y-hcpro-suppression-of-antiviral-silencing-in-nicotiana-benthamiana-plants-correlates-with-its-ability-to-bind-in-vivo-to-21-and-22-nucleotide-small-rnas-of-viral-sequence
#6
Francisco J Del Toro, Livia Donaire, Emmanuel Aguilar, Bong-Nam Chung, Francisco Tenllado, Tomás Canto
We have investigated short and small RNAs (sRNAs) that were bound to a biologically active hexahistidine-tagged Potato virus Y (PVY) HCPro suppressor of silencing, expressed from a heterologous virus vector in Nicotiana benthamiana plants, and purified under non-denaturing conditions. We found that RNAs in purified preparations were differentially enriched in sRNAs of 21 and to a much lesser extent of 22 nucleotides (nt) in length and of viral sequence (vsRNAs) when compared to those found in a control plant protein background bound to the nickel resin in the absence of HCPro, or in a purified alanine substitution HCPro mutant (HCPro mutB) control that lacked suppressor of silencing activity...
April 5, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28381556/poly-c-binding-protein-1-pcbp1-regulates-skeletal-muscle-differentiation-by-modulating-microrna-processing-in-myoblasts
#7
Ramon A Espinoza-Lewis, Qiumei Yang, Jianming Liu, Zhan-Peng Huang, Xiaoyun Hu, Daiwen Chen, Da-Zhi Wang
Control of muscle cell proliferation and differentiation is essential to proper muscle development, function, and regeneration, and numerous transcriptional and post-transcriptional regulators are key to these processes. For example, recent studies have linked microRNAs (miRNAs) to muscle gene expression, development, and disease. The poly(C)-binding protein1 (Pcbp1, hnRNP-E1, or αCP-1) has been reported to bind the 3'UTRs of target genes to regulate mRNA stability and protein translation. However, Pcbp1's biological function in skeletal muscle and general mechanism of action remain largely undetermined...
April 5, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28369725/rna-polymerase-i-inhibition-with-cx-5461-as-a-novel-therapeutic-strategy-to-target-myc-in-multiple-myeloma
#8
Hans C Lee, Hua Wang, Veerabhadran Baladandayuthapani, Heather Lin, Jin He, Richard J Jones, Isere Kuiatse, Dongmin Gu, Zhiqiang Wang, Wencai Ma, John Lim, Sean O'Brien, Jonathan Keats, Jing Yang, Richard E Davis, Robert Z Orlowski
Dysregulation of MYC is frequently implicated in both early and late myeloma progression events, yet its therapeutic targeting has remained a challenge. Among key MYC downstream targets is ribosomal biogenesis, enabling increases in protein translational capacity necessary to support the growth and self-renewal programmes of malignant cells. We therefore explored the selective targeting of ribosomal biogenesis with the small molecule RNA polymerase (pol) I inhibitor CX-5461 in myeloma. CX-5461 induced significant growth inhibition in wild-type (WT) and mutant TP53 myeloma cell lines and primary samples, in association with increases in downstream markers of apoptosis...
April 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28352639/racial-differences-in-expression-levels-of-mirna-machinery-related-genes-dicer-drosha-dgcr8-and-ago2-in-asian-korean-papillary-thyroid-carcinoma-and-comparative-validation-using-the-cancer-genome-atlas
#9
Jaegil Kim, Woo-Jae Park, Kwang-Joon Jeong, Sun Hee Kang, Sun Young Kwon, Shin Kim, Jong-Wook Park
Aberrant regulation of microRNA (miRNA) machinery components is associated with various human cancers, including papillary thyroid carcinoma (PTC), which is the most common type of thyroid cancer, and a higher prevalent female malignancy. The purpose of this study is to investigate racial differences in mRNA expression levels of four miRNA machinery components, Dicer, Drosha, DGCR8, and AGO2, and their correlations with clinicopathological characteristics. Forty PTC samples from female Asian Korean PTC patients were enrolled...
2017: International Journal of Genomics
https://www.readbyqxmd.com/read/28340815/expression-profile-of-microrna-biogenesis-components-in-renal-transplant-patients
#10
E Celen, M G Ertosun, H Kocak, A Dinckan, B Yoldas
BACKGROUND: MicroRNAs (miRNAs) and the miRNA biogenesis components are potential biomarkers of some prevalent diseases, such as cancer and diabetes. In light of this information, we aimed to investigate the expression profiles of miRNA biogenesis components in renal transplant patients before and after transplantation and how these profiles are related to immunosuppressive treatment and clinical outcomes of these patients. METHODS: In this study, gene and protein expression profiles of Dicer, Drosha, Pasha (DGCR8), Exportin5 (XPO5), and Argonaute2 (AGO2) in peripheral blood mononuclear cells (PBMCs) of renal transplant patients were evaluated by means of real-time quantitative polymerase chain reaction and Western blot methods before and 3 months after transplantation...
April 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28334781/auf1-facilitates-microrna-mediated-gene-silencing
#11
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/28326190/malat1-regulates-myogenic-differentiation-and-muscle-regeneration-through-modulating-myod-transcriptional-activity
#12
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/28319084/structural-and-mechanistic-insights-into-an-archaeal-dna-guided-argonaute-protein
#13
Sarah Willkomm, Christine A Oellig, Adrian Zander, Tobias Restle, Ronan Keegan, Dina Grohmann, Sabine Schneider
Argonaute (Ago) proteins in eukaryotes are known as key players in post-transcriptional gene silencing(1), while recent studies on prokaryotic Agos hint at their role in the protection against invading DNA(2,3). Here, we present crystal structures of the apo enzyme and a binary Ago-guide complex of the archaeal Methanocaldococcus jannaschii (Mj) Ago. Binding of a guide DNA leads to large structural rearrangements. This includes the structural transformation of a hinge region containing a switch helix, which has been shown for human Ago2 to be critical for the dynamic target search process(4-6)...
March 20, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28300636/perinatal-protein-malnutrition-alters-expression-of-mirna-biogenesis-genes-xpo5-and-ago2-in-mice-brain
#14
Bruno G Berardino, Estefanía A Fesser, Eduardo T Cánepa
Due to its widespread incidence, maternal malnutrition remains one of the major non-genetic factors affecting the development of newborn's brain. While all nutrients have certain influence on brain maturation, proteins appear to be the most critical for the development of neurological functions. An increasing number of studies point out that the effects of early-life nutritional inadequacy has long lasting effects on the brain and lead to permanent deficits in learning and behavior. Epigenetic mechanisms provide a potential link between the nutrition status during critical periods and changes in gene expression that may lead to disease phenotypes...
March 11, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28270624/abscisic-acid-induces-resistance-against-bamboo-mosaic-virus-through-argonaute-2-and-3
#15
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/28228215/hnrnpk-regulated-ptov1-as1-modulates-heme-oxygenase-1-expression-via-mir-1207-5p
#16
Chang Hoon Shin, Seongho Ryu, Hyeon Ho Kim
Antisense transcripts were initially identified as transcriptional noise, but have since been reported to play an important role in the quality control of miRNA functions. In this report, we tested the hypothesis that hnRNPK regulates miRNA function via competitive endogenous RNAs, such as pseudogenes, long non-coding RNAs, and antisense transcripts. Based on analyses of RNA sequencing data, the knockdown of hnRNPK decreased antisense PTOV1-AS1 transcript, which harbors five binding sites for miR-1207-5p. We identified heme oxygenase-1 (HO-1) mRNA as a novel target of miR-1207-5p by western blotting and Ago2 immunoprecipitation...
February 23, 2017: BMB Reports
https://www.readbyqxmd.com/read/28223440/idn2-interacts-with-rpa-and-facilitates-dna-double-strand-break-repair-by-homologous-recombination-in-arabidopsis
#17
Mingming Liu, Zhaoqing Ba, Pedro Costa-Nunes, Wei Wei, Lanxia Li, Fansi Kong, Yan Li, Jijie Chai, Olga Pontes, Yijun Qi
Repair of DNA double-strand breaks (DSBs) is critical for the maintenance of genome integrity. We previously showed that DSB-induced small RNAs (diRNAs) facilitate homologous recombination-mediated DSB repair in Arabidopsis thaliana Here, we show that INVOLVED IN DE NOVO2 (IDN2), a double-stranded RNA binding protein involved in small RNA-directed DNA methylation, is required for DSB repair in Arabidopsis. We find that IDN2 interacts with the heterotrimeric replication protein A (RPA) complex. Depletion of IDN2 or the diRNA binding ARGONAUTE2 leads to increased accumulation of RPA at DSB sites and mislocalization of the recombination factor RAD51...
March 2017: Plant Cell
https://www.readbyqxmd.com/read/28163933/analysis-of-argonaute-complex-bound-mrnas-in-du145-prostate-carcinoma-cells-reveals-new-mirna-target-genes
#18
Jaroslaw Szczyrba, Volker Jung, Michaela Beitzinger, Elke Nolte, Sven Wach, Martin Hart, Sandra Sapich, Marc Wiesehöfer, Helge Taubert, Gunther Wennemuth, Norbert Eichner, Thomas Stempfl, Bernd Wullich, Gunter Meister, Friedrich A Grässer
Posttranscriptional gene regulation by microRNAs (miRNAs) contributes to the induction and maintenance of prostate carcinoma (PCa). To identify mRNAs enriched or removed from Ago2-containing RISC complexes, these complexes were immunoprecipitated from normal prostate fibroblasts (PNFs) and the PCa line DU145 and the bound mRNAs were quantified by microarray. The analysis of Ago complexes derived from PNFs or DU145 confirmed the enrichment or depletion of a variety of mRNAs already known from the literature to be deregulated...
2017: Prostate Cancer
https://www.readbyqxmd.com/read/28148824/biochemical-and-genetic-functional-dissection-of-the-p38-viral-suppressor-of-rna-silencing
#19
Taichiro Iki, Marie-Aude Tschopp, Olivier Voinnet
Phytoviruses encode viral suppressors of RNA-silencing (VSRs) to counteract the plant antiviral silencing response, which relies on virus-derived small interfering (si)RNAs processed by Dicer RNaseIII enzymes and subsequently loaded into ARGONAUTE (AGO) effector proteins. Here, a tobacco cell-free system was engineered to recapitulate the key steps of antiviral RNA-silencing and, in particular, the most upstream double-stranded (ds)RNA processing reaction, not kinetically investigated thus far in the context of plant VSR studies...
February 1, 2017: RNA
https://www.readbyqxmd.com/read/28127848/mir-30c-protects-diabetic-nephropathy-by-suppressing-epithelial-to-mesenchymal-transition-in-db-db-mice
#20
Yanru Zhao, Zhongwei Yin, Huaping Li, Jiahui Fan, Shenglan Yang, Chen Chen, Dao Wen Wang
Epithelial-to-mesenchymal transition (EMT) plays a significant role in tubulointerstitial fibrosis, which is a hallmark of diabetic nephropathy. Thus, identifying the mechanisms of EMT activation could be meaningful. In this study, loss of miR-30c accompanied with increased EMT was observed in renal tubules of db/db mice and cultured HK2 cells exposed to high glucose. To further explore the roles of miR-30c in EMT and tubulointerstitial fibrosis, recombinant adeno-associated viral vector was applied to manipulate the expression of miR-30c...
April 2017: Aging Cell
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