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https://www.readbyqxmd.com/read/28636969/human-virus-derived-small-rnas-can-confer-antiviral-immunity-in-mammals
#1
Yang Qiu, Yanpeng Xu, Yao Zhang, Hui Zhou, Yong-Qiang Deng, Xiao-Feng Li, Meng Miao, Qiang Zhang, Bo Zhong, Yuanyang Hu, Fu-Chun Zhang, Ligang Wu, Cheng-Feng Qin, Xi Zhou
RNA interference (RNAi) functions as a potent antiviral immunity in plants and invertebrates; however, whether RNAi plays antiviral roles in mammals remains unclear. Here, using human enterovirus 71 (HEV71) as a model, we showed HEV71 3A protein as an authentic viral suppressor of RNAi during viral infection. When the 3A-mediated RNAi suppression was impaired, the mutant HEV71 readily triggered the production of abundant HEV71-derived small RNAs with canonical siRNA properties in cells and mice. These virus-derived siRNAs were produced from viral dsRNA replicative intermediates in a Dicer-dependent manner and loaded into AGO, and they were fully active in degrading cognate viral RNAs...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636953/dicer-deficiency-differentially-impacts-microglia-of-the-developing-and-adult-brain
#2
Diana Varol, Alexander Mildner, Thomas Blank, Anat Shemer, Neta Barashi, Simon Yona, Eyal David, Sigalit Boura-Halfon, Yifat Segal-Hayoun, Louise Chappell-Maor, Hadas Keren-Shaul, Dena Leshkowitz, Eran Hornstein, Martin Fuhrmann, Ido Amit, Nicola Maggio, Marco Prinz, Steffen Jung
Microglia seed the embryonic neuro-epithelium, expand and actively sculpt neuronal circuits in the developing central nervous system, but eventually adopt relative quiescence and ramified morphology in the adult. Here, we probed the impact of post-transcriptional control by microRNAs (miRNAs) on microglial performance during development and adulthood by generating mice lacking microglial Dicer expression at these distinct stages. Conditional Dicer ablation in adult microglia revealed that miRNAs were required to limit microglial responses to challenge...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28627619/expression-of-dicer-in-rheumatoid-arthritis-is-associated-with-disease-activity-and-balances-the-production-of-tnf%C3%A2-%C3%AE
#3
Shujun Wang, Min Yuan, Lijun Song, Xiuying Zhang, Qin Geng, Hongju Zhang, Xingfu Li
Gene expression can be altered through RNA interference (RNAi), including microRNA (miRNA) or small interfering RNA. Alterations of miRNAs in rheumatoid arthritis (RA) have been reported, however, the components of the RNAi machinery in RA remain to be fully elucidated. The aim of the present study was to detect the levels of Dicer, Argonaute2 and Drosha, components of the RNAi machinery, in the peripheral blood mononuclear cells of patients with RAusingreverse transcription‑quantitative polymerase chain reaction, and to compare the results with disease activity and clinical features...
June 9, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28624536/microrna-dependent-regulation-of-metamorphosis-and-identification-of-micrornas-in-the-red-flour-beetle-tribolium-castaneum
#4
Wei Wu, Wenfeng Xiong, Chengjun Li, Mengfan Zhai, Yao Li, Fei Ma, Bin Li
To date, although some microRNAs (miRNAs) have been discovered in the holometabolism insect Tribolium castaneum, large numbers of miRNAs still require investigation. Knocking down Dicer-1 (Dcr-1) and Argonaute-1 (Ago-1) in late larvae impaired miRNA synthesis, affected the juvenile hormone pathway by up-regulating Methoprene-tolerant (Met) and Krüppel-homolog1 (Kr-h1) transcript levels, and resulted in a series of defects in T. castaneum development and metamorphosis. Thus, high-throughput Illumina/Solexa sequencing was performed with a mixed sample of eight key developmental stages of T...
June 14, 2017: Genomics
https://www.readbyqxmd.com/read/28621425/epigenetic-mechanism-of-fmr1-inactivation-in-fragile-x-syndrome
#5
Merav Hecht, Amalia Tabib, Tamar Kahan, Shari Orlanski, Michal Gropp, Yuval Tabach, Ofra Yanuka, Nissim Benvenisty, Ilana Keshet, Howard Cedar
Fragile X syndrome is the most frequent cause of inherited intellectual disability. The primary molecular defect in this disease is the expansion of a CGG repeat in the 5' region of the fragile X mental retardation1 (FMR1) gene, leading to de novo methylation of the promoter and inactivation of this otherwise normal gene, but little is known about how these epigenetic changes occur during development. In order to gain insight into the nature of this process, we have used cell fusion technology to recapitulate the events that occur during early embryogenesis...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/28611386/effects-of-transient-high-temperature-treatment-on-the-intestinal-flora-of-the-silkworm-bombyx-mori
#6
Zhenli Sun, Dhiraj Kumar, Guangli Cao, Liyuan Zhu, Bo Liu, Min Zhu, Zi Liang, Sulan Kuang, Fei Chen, Yongjie Feng, Xiaolong Hu, Renyu Xue, Chengliang Gong
The silkworm Bombyx mori is a poikilotherm and is therefore sensitive to various climatic conditions. The influence of temperature on the intestinal flora and the relationship between the intestinal flora and gene expression in the silkworm remain unknown. In the present study, changes of the intestinal flora at 48, 96 and 144 h following transient high temperature treatment (THTT) of 37 °C for 8 h were investigated. According to principal component analysis, the abundances of Enterococcus and Staphylococcus showed a negative correlation with other dominant genera...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28608842/talaromyces-marneffei-genomic-transcriptomic-proteomic-and-metabolomic-studies-reveal-mechanisms-for-environmental-adaptations-and-virulence
#7
REVIEW
Susanna K P Lau, Chi-Ching Tsang, Patrick C Y Woo
Talaromycesmarneffei is a thermally dimorphic fungus causing systemic infections in patients positive for HIV or other immunocompromised statuses. Analysis of its ~28.9 Mb draft genome and additional transcriptomic, proteomic and metabolomic studies revealed mechanisms for environmental adaptations and virulence. Meiotic genes and genes for pheromone receptors, enzymes which process pheromones, and proteins involved in pheromone response pathway are present, indicating its possibility as a heterothallic fungus...
June 13, 2017: Toxins
https://www.readbyqxmd.com/read/28599275/dicer-suppresses-cytoskeleton-remodeling-and-tumorigenesis-of-colorectal-epithelium-by-mir-324-5p-mediated-suppression-of-hmgxb3-and-wasf-2
#8
Li Na Sun, Cheng Xing, Zheng Zhi, Yao Liu, Liang-Yan Chen, Tong Shen, Qun Zhou, Yu Hong Liu, Wen Juan Gan, Jing-Ru Wang, Yong Xu, Jian Ming Li
Emerging evidence indicates that microRNAs, a class of small and well-conserved noncoding RNAs, participate in many physiological and pathological processes. RNase III endonuclease DICER is one of the key enzymes for microRNA biogenesis. Here, we found that DICER was downregulated in tumor samples of colorectal cancer (CRC) patients at both mRNA and protein levels. Importantly, intestinal epithelial cell (IEC)-specific deletion of Dicer mice got more tumors after azoxymethane and dextran sulfate sodium (DSS) administration...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28598829/impaired-expression-of-drosha-in-breast%C3%A2-cancer
#9
Ali Akbar Poursadegh Zonouzi, Mohammad Shekari, Azim Nejatizadeh, Samira Shakerizadeh, Hedieh Fardmanesh, Ahmad Poursadegh Zonouzi, Mohammad Rahmati-Yamchi, Majid Tozihi
BACKGROUND: Impaired miRNAs processing pathway is one interesting scenario for global downregulation of the miRNAome in various types of malignancy. We previously reported that DGCR8 and Dicer genes dysregulated in patients with breast cancer. OBJECTIVE: To evaluate the expression pattern of Drosha in patients with breast cancer. METHODS: We evaluated the mRNA expression level of Drosha in 70 fresh breast carcinomas and adjacent non-neoplastic tissue using quantitative real-time PCR and assessed the possible correlation between its expression and clinicopathological parameters...
June 2, 2017: Breast Disease
https://www.readbyqxmd.com/read/28584057/an-rnai-based-high-throughput-screening-assay-to-identify-small-molecule-inhibitors-of-hepatitis-b-virus-replication
#10
Subhanita Ghosh, Abhinav Kaushik, Sachin Khurana, Aditi Varshney, Avishek Kumar Singh, Pradeep Dahiya, Jitendra K Thakur, Shiv Kumar Sarin, Dinesh Gupta, Pawan Malhotra, Sunil K Mukherjee, Raj K Bhatnagar
Persistent or chronic infection with the hepatitis B virus represents one of the most common viral diseases in humans. The hepatitis B virus deploys the Hepatitis B Virus X Protein (HBx) as a suppressor of host defenses consisting of RNAi-based silencing of viral genes. Because of its critical role in countering host defenses, HBx represents an attractive target for antiviral drugs. Here, we developed and optimized a loss-of-function screening procedure, which identified a potential pharmacophore that abrogated HBxs RNAi suppression activity...
June 5, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28571917/targeting-mir-21-with-sophocarpine-inhibits-tumor-progression-and-reverses-epithelial-mesenchymal-transition-in-head-and-neck-cancer
#11
Wei Liu, Beilei Zhang, Guo Chen, Wenjiao Wu, Lin Zhou, Yaru Shi, Qi Zeng, Yanqiu Li, Youwei Sun, Xingming Deng, Fu Wang
A major challenge for cancer chemotherapy is the development of safe and clinically effective chemotherapeutic agents. With its low toxicity profile, sophocarpine (SC), a naturally occurring tetracyclic quinolizidine alkaloid derived from Sophora alopecuroides L, has shown promising therapeutic properties, including anti-inflammatory, anti-nociceptive, and antivirus activities. However, the antitumor efficacy of SC and its underlying mechanisms have not been completely delineated. In the present study, the inhibitory effect of SC on head and neck squamous cell carcinoma (HNSCC) progression and possible mechanisms for this effect involving microRNA-21 (miR-21) regulation were investigated...
May 29, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28569591/influence-of-the-loop-size-and-nucleotide-composition-on-agoshrna-biogenesis-and-activity
#12
Elena Herrera-Carrillo, Alex Harwig, Ben Berkhout
Short hairpin RNAs (shRNAs) are widely used for gene silencing by the RNA interference (RNAi) mechanism. The shRNA precursor is processed by the Dicer enzyme into active small interfering RNAs (siRNAs) that subsequently target a complementary mRNA for cleavage by the Argonaute 2 (Ago2) complex. Recent evidence indicates that shRNAs with a relatively short basepaired stem bypass Dicer and are instead processed by Ago2. We termed these molecules AgoshRNAs as both processing and silencing steps are mediated by Ago2 and proposed rules for the design of effective AgoshRNA molecules...
June 1, 2017: RNA Biology
https://www.readbyqxmd.com/read/28558690/profile-and-functional-analysis-of-small-rnas-derived-from-aspergillus-fumigatus-infected-with-double-stranded-rna-mycoviruses
#13
Selin Özkan, Irina Mohorianu, Ping Xu, Tamas Dalmay, Robert H A Coutts
BACKGROUND: Mycoviruses are viruses that naturally infect and replicate in fungi. Aspergillus fumigatus, an opportunistic pathogen causing fungal lung diseases in humans and animals, was recently shown to harbour several different types of mycoviruses. A well-characterised defence against virus infection is RNA silencing. The A. fumigatus genome encodes essential components of the RNA silencing machinery, including Dicer, Argonaute and RNA-dependent RNA polymerase (RdRP) homologues. Active silencing of double-stranded (ds)RNA and the generation of small RNAs (sRNAs) has been shown for several mycoviruses and it is anticipated that a similar mechanism will be activated in A...
May 30, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28555079/muc1-inhibition-leads-to-decrease-in-pd-l1-levels-via-up-regulation-of-mirnas
#14
A R Pyzer, D Stroopinsky, J Rosenblatt, E Anastasiadou, H Rajabi, A Washington, A Tagde, J-H Chu, M Coll, A L Jiao, L T Tsai, D E Tenen, L Cole, K Palmer, A Ephraim, R K Leaf, M Nahas, A Apel, Mb-N Zommer, S Jain, M McMasters, L Mendez, J Arnason, B A Raby, F Slack, D Kufe, D Avigan
The PD-L1/PD-1 pathway is a critical component of the immunosuppressive tumor microenvironment in AML, but little is known about its regulation. We investigated the role of the MUC1 oncoprotein in modulating PD-L1 expression in AML. Silencing of MUC1 in AML cell lines suppressed PD-L1 expression without a decrease in PD-L1 mRNA levels, suggesting a post-transcriptional mechanism of regulation. We identified the microRNAs miR-200c and miR-34a as key regulators of PD-L1 expression in AML. Silencing of MUC1 in AML cells led to a marked increase in miR-200c and miR-34a levels, without changes in precursor microRNA, suggesting that MUC1 might regulate microRNA processing...
May 30, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28553929/silencing-of-hiv-1-by-agoshrna-molecules
#15
E Herrera-Carrillo, A Harwig, B Berkhout
RNA interference (RNAi) is a sequence-specific gene silencing mechanism that is triggered by the expression of a short hairpin RNA (shRNA). shRNA molecules enter the RNAi pathway at the Dicer processing step. Recent studies indicated that the cellular microRNA (miRNA) miR-451 is not recognized by Dicer, but that is processed instead by the Argonaute 2 (Ago2) protein. Subsequently, Dicer-independent shRNAs were described that rely on Ago2 for processing as well as the subsequent silencing step. We called these AgoshRNA molecules because they depend on Ago2 both for maturation and activation...
May 29, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28542524/ectopically-expressed-slc34a2a-sense-antisense-transcripts-cause-a-cerebellar-phenotype-in-zebrafish-embryos-depending-on-rna-complementarity-and-dicer
#16
Monica J Piatek, Victoria Henderson, Amy Fearn, Bill Chaudhry, Andreas Werner
Natural antisense transcripts (NATs) are complementary to protein coding genes and potentially regulate their expression. Despite widespread occurrence of NATs in the genomes of higher eukaryotes, their biological role and mechanism of action is poorly understood. Zebrafish embryos offer a unique model system to study sense-antisense transcript interplay at whole organism level. Here, we investigate putative antisense transcript-mediated mechanisms by ectopically co-expressing the complementary transcripts during early zebrafish development...
2017: PloS One
https://www.readbyqxmd.com/read/28542329/novel-agoshrna-molecules-for-silencing-of-the-ccr5-co-receptor-for-hiv-1-infection
#17
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/28542273/expression-profile-of-epstein-barr-virus-and-human-adenovirus-small-rnas-in-tonsillar-b-and-t-lymphocytes
#18
Farzaneh Assadian, Wael Kamel, Göran Laurell, Catharina Svensson, Tanel Punga, Göran Akusjärvi
We have used high-throughput small RNA sequencing to characterize viral small RNA expression in purified tonsillar B and T lymphocytes isolated from patients tested positive for Epstein-Barr virus (EBV) or human adenovirus (HAdV) infections, respectively. In the small set of patients analyzed, the expression profile of EBV and HAdV miRNAs could not distinguish between patients diagnosed with tonsillar hypertrophy or chronic/recurrent tonsillitis. The EBV miR-BART expression profile among the patients diagnosed with tonsillar diseases resembles most closely the pattern seen in EBV+ tumors (Latency II/I)...
2017: PloS One
https://www.readbyqxmd.com/read/28542144/dicer-and-micrornas-protect-adult-dopamine-neurons
#19
Piotr Chmielarz, Julia Konovalova, Syeda Sadia Najam, Heike Alter, Timo Petteri Piepponen, Holger Erfle, Kai C Sonntag, Günther Schütz, Ilya A Vinnikov, Andrii Domanskyi
MicroRNAs (miRs) are important post-transcriptional regulators of gene expression implicated in neuronal development, differentiation, aging and neurodegenerative diseases, including Parkinson's disease (PD). Several miRs have been linked to PD-associated genes, apoptosis and stress response pathways, suggesting that deregulation of miRs may contribute to the development of the neurodegenerative phenotype. Here, we investigate the cell-autonomous role of miR processing RNAse Dicer in the functional maintenance of adult dopamine (DA) neurons...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28540674/microrna-expression-protein-participants-in-microrna-regulation
#20
Valeria M King, Glen M Borchert
MiRNAs are ~20 nt small RNAs that regulate networks of proteins using a seed region of nucleotides 2-8 to complement the 3' UTR of target mRNAs. The biogenesis and function of miRNAs as translational repressors is facilitated by protein counterparts that process primary and precursor miRNAs to maturity (Drosha/DCGR8 and Dicer/TRBP respectively) and incorporate miRNAs into the protein complex RISC to recognize and repress target mRNAs (RISC proteins: Ago/TRBP1/TRBP2/DICER). Similarly, siRNAs through comparable mechanisms are loaded into the protein complex RITS to heterochromatin formation of DNA and suppress transcription of particular genes...
2017: Methods in Molecular Biology
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