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https://www.readbyqxmd.com/read/28542329/novel-agoshrna-molecules-for-silencing-of-the-ccr5-co-receptor-for-hiv-1-infection
#1
Elena Herrera-Carrillo, Ben Berkhout
Allogeneic transplantation of blood stem cells from a CCR5-Δ32 homozygous donor to an HIV-infected individual, the "Berlin patient", led to a cure. Since then there has been a search for approaches that mimic this intervention in a gene therapy setting. RNA interference (RNAi) has evolved as a powerful tool to regulate gene expression in a sequence-specific manner and can be used to inactivate the CCR5 mRNA. Short hairpin RNA (shRNA) molecules can impair CCR5 expression, but these molecules may cause unintended side effects and they will not be processed in cells that lack Dicer, such as monocytes...
2017: PloS One
https://www.readbyqxmd.com/read/28539638/salmonella-produce-microrna-like-rna-fragment-sal-1-in-the-infected-cells-to-facilitate-intracellular-survival
#2
Hongwei Gu, Chihao Zhao, Tianfu Zhang, Hongwei Liang, Xiao-Ming Wang, Yi Pan, Xi Chen, Quan Zhao, Donghai Li, Fenyong Liu, Chen-Yu Zhang, Ke Zen
Salmonella have developed a sophisticated machinery to evade immune clearance and promote survival in the infected cells. Previous studies were mostly focused on either bacteria itself or host cells, the interaction mechanism of host-pathogen awaits further exploration. In the present study, we show that Salmonella can exploit mammalian cell non-classical microRNA processing machinery to further process bacterial small non-coding RNAs into microRNA-like fragments. Sal-1, one such fragment with the highest copy number in the infected cells, is derived from Salmonella 5'-leader of the ribosomal RNA transcript and has a 'stem' structure-containing precursor...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28539410/leishmania-donovani-restricts-mitochondrial-dynamics-to-enhance-mirnp-stability-and-target-rna-repression-in-host-macrophages
#3
Yogaditya Chakrabarty, Suvendra N Bhattacharyya
microRNAs (miRNA), the tiny regulatory RNAs, form complex with Argonaute (Ago) proteins and inhibit gene expression in metazoan cells. While studying parasite invaded macrophages, we have identified a unique mode of gene regulation, where the parasite Leishmania donovani (Ld) causes mitochondrial depolarization, reduces mitochondrial dynamics and restricts turnover of cellular microRNA ribonucleoprotein (miRNP) complexes in infected host cells. This leads to increased stability of miRNPs along with elevated level of Ago2 bound cytokine mRNA in Ld infected macrophages...
May 24, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28520497/lncrna-pvt1-regulates-chondrocyte-apoptosis-in-osteoarthritis-by-acting-as-a-sponge-for-mir-488-3p
#4
Yufei Li, Shuhua Li, Yatong Luo, Yong Liu, Nanhui Yu
Long noncoding RNAs (lncRNAs) have been known to be involved in multiple diverse diseases, including osteoarthritis (OA). The present study aims at exploring the biological role of lncRNA plasmacytoma variant translocation 1 (PVT1) in OA and the underlying mechanism. Results showed that the expression of PVT1 was upregulated in OA chondrocytes compared with normal chondrocytes, silencing PVT1 inhibited the apoptosis of OA chondrocytes, and overexpression of PVT1 promoted the apoptosis of normal chondrocytes...
May 18, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28518140/a-mirna-101-3p-bim-axis-as-a-determinant-of-serum-deprivation-induced-endothelial-cell-apoptosis
#5
Ji-Hee Kim, Dong-Keon Lee, Joohwan Kim, Seunghwan Choi, Wonjin Park, Kwon-Soo Ha, Tae-Hoon Kim, Jongseon Choe, Moo-Ho Won, Young-Guen Kwon, Young-Myeong Kim
Serum deprivation or withdrawal induces apoptosis in endothelial cells, resulting in endothelial cell dysfunction that is associated with cardiovascular disease. However, there is still limited information on the role of miRNA in serum deprivation-induced apoptosis. Here we found that serum deprivation increased caspase-dependent apoptosis through miRNA-101-3p downregulation, without altering expression of its host gene RNA 3'-terminal phosphate cyclase-like 1, which was highly correlated with suppressed expression levels of Dicer and Argonaute 2 (Ago2), indicating that miR-101-3p is post-transcriptionally elevated in serum-deprived conditions...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28499009/a-viral-suppressor-of-rna-silencing-inhibits-argonaute-1-function-by-precluding-target-rna-binding-to-pre-assembled-risc
#6
Erzsébet Kenesi, Alberto Carbonell, Rita Lózsa, Beáta Vértessy, Lóránt Lakatos
In most eukaryotes, RNA silencing is an adaptive immune system regulating key biological processes including antiviral defense. To evade this response, viruses of plants, worms and insects have evolved viral suppressors of RNA silencing proteins (VSRs). Various VSRs, such as P1 from Sweet potato mild mottle virus (SPMMV), inhibit the activity of RNA-induced silencing complexes (RISCs) including an ARGONAUTE (AGO) protein loaded with a small RNA. However, the specific mechanisms explaining this class of inhibition are unknown...
May 12, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28497119/aedes-aegypti-piwi4-is-a-noncanonical-piwi-protein-involved-in-antiviral-responses
#7
Margus Varjak, Kevin Maringer, Mick Watson, Vattipally B Sreenu, Anthony C Fredericks, Emilie Pondeville, Claire L Donald, Jelle Sterk, Joy Kean, Marie Vazeille, Anna-Bella Failloux, Alain Kohl, Esther Schnettler
The small interfering RNA (siRNA) pathway is a major antiviral response in mosquitoes; however, another RNA interference pathway, the PIWI-interacting RNA (piRNA) pathway, has been suggested to be antiviral in mosquitoes. Piwi4 has been reported to be a key mediator of this response in mosquitoes, but it is not involved in the production of virus-specific piRNAs. Here, we show that Piwi4 associates with members of the antiviral exogenous siRNA pathway (Ago2 and Dcr2), as well as with proteins of the piRNA pathway (Ago3, Piwi5, and Piwi6) in an Aedes aegypti-derived cell line, Aag2...
May 2017: MSphere
https://www.readbyqxmd.com/read/28488892/dcp1a-and-gw182-induce-distinct-cellular-aggregates-and-have-different-effects-on-microrna-pathway
#8
Xiaohui Wang, Liang Chang, Huanru Wang, Airong Su, Zhiwei Wu
AIM: P-bodies are cytoplasmic foci composed of mRNAs and enzymes involved in mRNA degradation. P-bodies have been found to link to RNA interference and RNA decay mediated by microRNAs (miRNAs) and translational repression. Here, we aim to investigate different effects of overexpressed Dcp1a or GW182 on cytoplasmic aggregates formation and influence on miRNA pathway. RESULTS: Small RNAs were recruited into endogenous foci of P-bodies and aggregates formed by Dcpa1 and GW182 overexpression...
May 10, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28472401/wig1-is-crucial-for-ago2-mediated-acot7-mrna-silencing-via-mirna-dependent-and-independent-mechanisms
#9
Hyung Chul Lee, Seung Hee Jung, Hyun Jung Hwang, Donghee Kang, Supriyo De, Dawood B Dudekula, Jennifer L Martindale, Byungkyu Park, Seung Kuk Park, Eun Kyung Lee, Jeong-Hwa Lee, Sunjoo Jeong, Kyungsook Han, Heon Joo Park, Young-Gyu Ko, Myriam Gorospe, Jae-Seon Lee
RNA-binding proteins (RBPs) are involved in mRNA splicing, maturation, transport, translation, storage and turnover. Here, we identified ACOT7 mRNA as a novel target of human WIG1. ACOT7 mRNA decay was triggered by the microRNA miR-9 in a WIG1-dependent manner via classic recruitment of Argonaute 2 (AGO2). Interestingly, AGO2 was also recruited to ACOT7 mRNA in a WIG1-dependent manner in the absence of miR-9, which indicates an alternative model whereby WIG1 controls AGO2-mediated gene silencing. The WIG1-AGO2 complex attenuated translation initiation via an interaction with translation initiation factor 5B (eIF5B)...
May 3, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28432338/crispr-cas9-mediated-inactivation-of-argonaute-2-reveals-its-differential-involvement-in-antiviral-responses
#10
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
#11
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 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28404816/pick1-ca-2-sensor-modulates-nmda-receptor-dependent-microrna-mediated-translational-repression-in-neurons
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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