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https://www.readbyqxmd.com/read/27907888/a-novel-role-for-gsk3%C3%AE-as-a-modulator-of-drosha-microprocessor-activity-and-microrna-biogenesis
#1
Claire E Fletcher, Jack D Godfrey, Akifumi Shibakawa, Martin Bushell, Charlotte L Bevan
Regulation of microRNA (miR) biogenesis is complex and stringently controlled. Here, we identify the kinase GSK3β as an important modulator of miR biogenesis at Microprocessor level. Repression of GSK3β activity reduces Drosha activity toward pri-miRs, leading to accumulation of unprocessed pri-miRs and reduction of pre-miRs and mature miRs without altering levels or cellular localisation of miR biogenesis proteins. Conversely, GSK3β activation increases Drosha activity and mature miR accumulation. GSK3β achieves this through promoting Drosha:cofactor and Drosha:pri-miR interactions: it binds to DGCR8 and p72 in the Microprocessor, an effect dependent upon presence of RNA...
October 23, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27872619/ebola-vp40-in-exosomes-can-cause-immune-cell-dysfunction
#2
Michelle L Pleet, Allison Mathiesen, Catherine DeMarino, Yao A Akpamagbo, Robert A Barclay, Angela Schwab, Sergey Iordanskiy, Gavin C Sampey, Benjamin Lepene, Sergei Nekhai, M J Aman, Fatah Kashanchi
Ebola virus (EBOV) is an enveloped, ssRNA virus from the family Filoviridae capable of causing severe hemorrhagic fever with up to 80-90% mortality rates. The most recent outbreak of EBOV in West Africa starting in 2014 resulted in over 11,300 deaths; however, long-lasting persistence and recurrence in survivors has been documented, potentially leading to further transmission of the virus. We have previously shown that exosomes from cells infected with HIV-1, HTLV-1 and Rift Valley Fever virus are able to transfer viral proteins and non-coding RNAs to naïve recipient cells, resulting in an altered cellular activity...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27835943/precise-mapping-of-the-transcription-start-sites-of-human-micrornas-using-drosha-knockout-cells
#3
Geon Jeong, Yeong-Hwan Lim, Young-Kook Kim
BACKGROUND: The expression of microRNAs (miRNAs) is primarily regulated during their transcription. However, the transcriptional regulation of miRNA genes has not been studied extensively owing to the lack of sufficient information about the promoters and transcription start sites of most miRNAs. RESULTS: In this study, we identified the transcription start sites of human primary miRNAs (pri-miRNAs) using DROSHA knockout cells. DROSHA knockout resulted in increased accumulation of pri-miRNAs and facilitated the precise mapping of their 5' end nucleotides using the rapid amplification of cDNA ends (RACE) technique...
November 11, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27808570/dicer-and-drosha-gene-expression-and-polymorphisms-in-autoimmune-thyroid-diseases
#4
Minori Saeki, Mikio Watanabe, Naoya Inoue, Ena Tokiyoshi, Yukina Takuse, Yuya Arakawa, Yoh Hidaka, Yoshinori Iwatani
Dicer and Drosha are RNase III enzymes that are necessary for the biogenesis of most miRNAs. However, there are no reports on the association of Dicer and Drosha with the pathogenesis of autoimmune thyroid disease (AITD). We genotyped DICER rs3742330A/G and rs1057035T/C as well as DROSHA rs644236C/T and rs10719C/T polymorphisms in 255 Hashimoto's disease (HD) patients, in 255 Graves' disease (GD) patients and in 128 healthy controls by the polymerase chain reaction (PCR)- restriction fragment length polymorphism (RFLP) method...
November 3, 2016: Autoimmunity
https://www.readbyqxmd.com/read/27796942/comparison-of-mirna-profiling-during-airway-epithelial-repair-in-undifferentiated-and-differentiated-cells-in-vitro
#5
Wojciech Langwinski, Beata Narozna, Peter M Lackie, John W Holloway, Aleksandra Szczepankiewicz
Respiratory epithelium is a highly integrated structure that efficiently protects lungs from extrinsic irritants thanks to rapid repair of the wound. The repair is a complex process that requires coordinated expression of networks of genes. Plausible regulators of this process are microRNAs. We investigated whether global miRNA silencing influences the epithelial repair, and whether changes in miRNA expression profile during repair are similar between two bronchial epithelial cell cultures: differentiated and undifferentiated cells...
October 28, 2016: Journal of Applied Genetics
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
#6
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/27766492/co-and-no-bind-to-fe-ii-digeorge-critical-region-8-heme-but-do-not-restore-primary-microrna-processing-activity
#7
Judy P Hines, Aaron T Smith, Jose P Jacob, Gudrun S Lukat-Rodgers, Ian Barr, Kenton R Rodgers, Feng Guo, Judith N Burstyn
The RNA-binding heme protein DiGeorge critical region 8 (DGCR8) and its ribonuclease partner Drosha cleave primary transcripts of microRNA (pri-miRNA) as part of the canonical microRNA (miRNA) processing pathway. Previous studies show that bis-cysteine thiolate-coordinated Fe(III) DGCR8 supports pri-miRNA processing activity, while Fe(II) DGCR8 does not. In this study, we further characterized Fe(II) DGCR8 and tested whether CO or NO might bind and restore pri-miRNA processing activity to the reduced protein...
October 20, 2016: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/27762676/canonical-micrornas-enable-differentiation-protect-against-dna-damage-and-promote-cholesterol-biosynthesis-in-neural-stem-cells
#8
Zhong Liu, Cheng Zhang, Alireza Khodadadi-Jamayran, Lam Dang, Xiaosi Han, Kitai Kim, Hu Li, Rui Zhao
Neural stem cells (NSCs) have the capacity to differentiate into neurons, astrocytes, and oligodendrocytes, and therefore represent a promising donor tissue source for treating neurodegenerative diseases and repairing injuries of the nervous system. However, it remains unclear how canonical microRNAs (miRNAs), the subset of miRNAs requiring the Drosha-Dgcr8 microprocessor and the type III RNase Dicer for biogenesis, regulate NSCs. In this study, we established and characterized <i>Dgcr8</i><sup>-/-</sup> NSCs from conditionally <i>Dgcr8</i>-disrupted mouse embryonic brain...
October 20, 2016: Stem Cells and Development
https://www.readbyqxmd.com/read/27755613/computational-prediction-of-non-enzymatic-rna-degradation-patterns
#9
Agnieszka Rybarczyk, Paulina Jackowiak, Marek Figlerowicz, Jacek Blazewicz
Since the beginning of the 21st century, an increasing interest in the research of ribonucleic acids has been observed in response to a surprising discovery of the role that RNA molecules play in the biological systems. It was demonstrated that they do not only take part in the protein synthesis (mRNA, rRNA, tRNA) but also are involved in the regulation of gene expression. Several classes of small regulatory RNAs have been discovered (e.g. microRNA, small interfering RNA, piwiRNA). Most of them are excised from specific double-stranded RNA precursors by enzymes that belong to the RNaseIII family (Drosha, Dicer or Dicer-like proteins)...
October 19, 2016: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/27715458/alternative-splicing-of-a-viral-mirtron-differentially-affects-the-expression-of-other-micrornas-from-its-cluster-and-of-the-host-transcript
#10
Perrine Rasschaert, Thomas Figueroa, Ginette Dambrine, Denis Rasschaert, Sylvie Laurent
Interplay between alternative splicing and the Microprocessor may have differential effects on the expression of intronic miRNAs organised into clusters. We used a viral model - the LAT long non-coding RNA (LAT lncRNA) of Marek's disease oncogenic herpesvirus (MDV-1), which has the mdv1-miR-M8-M6-M7-M10 cluster embedded in its first intron - to assess the impact of splicing modifications on the biogenesis of each of the miRNAs from the cluster. Drosha silencing and alternative splicing of an extended exon 2 of the LAT lncRNA from a newly identified 3' splice site (SS) at the end of the second miRNA of the cluster showed that mdv1-miR-M6 was a 5'-tailed mirtron...
October 7, 2016: RNA Biology
https://www.readbyqxmd.com/read/27706675/letter-to-the-editor-drosha-dgcr8-and-dicer-mrnas-are-downregulated-in-human-cells-infected-with-dengue-virus-4-genet-mol-res-15-2-gmr-15027891-drosha-dicer-and-trbp-mrna-are-downregulated-in-vero-cells-with-the-3-utr-of-dengue-virus
#11
J A Castillo, S Urcuqui-Inchima
Dear Editor, A recent paper (Casseb et al., 2016) published in the journal Genetics and Molecular Research described the interesting concept that dengue virus (DENV)-4 infection, in the human cell line A-549, leads to the downregulation of expression of key components of microRNA (miRNA) biogenesis, such as Drosha, Dicer, and DGCR8. For this, the authors performed a time course infection of A-549 cells for 5 days. The highest viral load was observed at 3 days post-infection, which corresponded with the maximum downregulation of expression of Drosha, Dicer, and DGCR8, assayed by quantitative PCR (RT-qPCR)...
August 30, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27694906/crispr-cas9-targets-chicken-embryonic-somatic-cells-in-vitro-and-in-vivo-and-generates-phenotypic-abnormalities
#12
Kwaku Dad Abu-Bonsrah, Dongcheng Zhang, Donald F Newgreen
Chickens are an invaluable model for studying human diseases, physiology and especially development, but have lagged in genetic applications. With the advent of Programmable Engineered Nucleases, genetic manipulation has become efficient, specific and rapid. Here, we show that the CRISPR/Cas9 system can precisely edit the chicken genome. We generated HIRA, TYRP1, DICER, MBD3, EZH2, and 6 other gene knockouts in two chicken cell lines using the CRISPR/Cas9 system, with no off-target effects detected. We also showed that very large deletions (>75 kb) could be achieved...
October 3, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27641147/the-microprocessor-component-dgcr8-is-essential-for-early-b-cell-development-in-mice
#13
Andreas Brandl, Patrick Daum, Sven Brenner, Sebastian R Schulz, Desmond Yat-Hin Yap, Michael R Bösl, Jürgen Wittmann, Wolfgang Schuh, Hans-Martin Jäck
microRNAs (miRNAs) are important posttranscriptional regulators during hematopoietic lineage commitment and lymphocyte development. Mature miRNAs are processed from primary miRNA transcripts in two steps by the microprocessor complex, consisting of Drosha and its partner DiGeorge Critical Region 8 (DGCR8), and the RNAse III enzyme, Dicer. Conditional ablations of Drosha and Dicer have established the importance of both RNAses in B- and T-cell development. Here, we show that a cre-mediated B-cell specific deletion of DGCR8 in mice results in a nearly complete maturation block at the transition from the pro-B to the pre-B cell stage, and a failure to upregulate Ig μ heavy chain expression in pro-B cells...
October 5, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27636105/ikk%C3%AE-mediated-biogenesis-of-mir-196a-through-interaction-with-drosha-regulates-the-sensitivity-of-cancer-cells-to-radiotherapy
#14
X Fang, J-H Jeong, X Long, S-J Park, D Wang, M Shuai, R Wei, C Li, S Li, S Zhang, M B Duran, K-W Lo, S W Tsao, R Glaser, Z Luo, X Feng, Y Tian, J-L Luo
No abstract text is available yet for this article.
September 16, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27611467/variation-in-the-dicer-and-ran-genes-are-associated-with-survival-in-patients-with-hepatocellular-carcinoma
#15
Mi Na Kim, Jung Oh Kim, Seung Min Lee, Hana Park, Ju Ho Lee, Kyu Sung Rim, Seong Gyu Hwang, Nam Keun Kim
Single-nucleotide polymorphisms (SNPs) in microRNA machinery genes might affect microRNA processing and subsequently impact tumorigenesis. The aim of this study was to investigate the associations between SNPs in microRNA machinery genes and hepatocellular carcinoma (HCC) in a Korean population. Genotyping of six SNPs in microRNA machinery genes was performed using blood samples from 147 patients with HCC and 209 healthy control subjects. None of the six SNPs in microRNA machinery genes were significantly associated with HCC development...
2016: PloS One
https://www.readbyqxmd.com/read/27609577/-knockdown-of-drosha-promotes-chemosensitivity-of-epirubicin-for-gastric-cancer-mgc-803-cells
#16
Liyun Xu, Yanlin Chen, Siyang Wen, Yan'e DU, Xi Tang, Manran Liu
Objective To establish a gastric cancer cell line with stable Drosha silenced and explore the effect of Drosha on the chemosensitivity of gastric cancer cells to epirubicin. Methods Interfering sequences targeting Drosha were designed and inserted into the lentiviral vectors, which were used to transfect MGC-803 cells. The level of Drosha mRNA was detected by quantitative real-time PCR; Drosha protein was detected by Western blotting; MTT assay was performed to test the 50% inhibitory concentration (IC50) of epirubicin agaisnt wide-type MGC-803 cells...
September 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/27586307/ddx3x-promotes-the-biogenesis-of-a-subset-of-mirnas-and-the-potential-roles-they-played-in-cancer-development
#17
Luqing Zhao, Yitao Mao, Yuelong Zhao, Yanong He
DDX3X, located on the X-chromosome, belongs to the DEAD-box RNA helicase family and acts as a key RNA-binding protein to exert its regulatory functions in various biological processes. In this paper, knock-down the expression of DDX3X can affect a subset of miRNA expression levels, especially for miR-1, miR-141, miR-145, miR-19b, miR-20a and miR-34a. Through adopting the immunoprecipitation (IP), RNA immunoprecipitation (RIP), dual luciferase reporter assays, we illustrate that DDX3X could interact with Drosha/DGCR8 complex, elevate the processing activity of Drosha/DGCR8 complex on pri-miRNAs, and increase mature miRNA expression levels...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27565737/negative-feedback-circuitry-between-mir143hg-and-rbm24-in-hirschsprung-disease
#18
Chunxia Du, Ziyang Shen, Rujin Zang, Hua Xie, Hongxing Li, Pingfa Chen, Bo Hang, Xiaoqun Xu, Weibing Tang, Yankai Xia
Hirschsprung disease (HSCR) is a genetic disorder of neural crest development. It is also believed that epigenetic changes plays a role in the progression of this disease. Here we show that the MIR143 host gene (MIR143HG), the precursor of miR-143 and miR-145, decreased cell proliferation and migration and forms a negative feedback loop with RBM24 in HSCR. As RBM24 mRNA is a target of miR-143, upregulation of RBM24 upon an increase in the level of MIR143HG could be attributed to sequestration of miR-143 by MIR143HG (sponge effect)...
November 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27560640/progress-in-micro-rna-focused-research-in-endocrinology
#19
K Voglova, J Bezakova, Iveta Herichova
Micro RNAs (miRNAs) are small regulatory molecules of increasing biologists' interest. miRNAs, unlikely mRNA, do not encode proteins. It is a class of small double stranded RNA molecules that via their seed sequence interact with mRNA and inhibit its expression. It has been estimated that 30% of human gene expression is regulated by miRNAs. One miRNA usually targets several mRNAs and one mRNA can be regulated by several miRNAs. miRNA biogenesis is realized by key enzymes, Drosha and Dicer. miRNA/mRNA interaction depends on binding to RNA-induced silencing complex...
April 2016: Endocrine Regulations
https://www.readbyqxmd.com/read/27546061/analysis-of-heme-iron-coordination-in-dgcr8-the-heme-binding-component-of-the-microprocessor-complex
#20
Hazel M Girvan, Justin M Bradley, Myles R Cheesman, James R Kincaid, Yilin Liu, Kazimierz Czarnecki, Karl Fisher, David Leys, Stephen E J Rigby, Andrew W Munro
DGCR8 is the RNA-binding partner of the nuclease Drosha. Their complex (the "Microprocessor") is essential for processing of long, primary microRNAs (pri-miRNAs) in the nucleus. Binding of heme to DGCR8 is essential for pri-miRNA processing. On the basis of the split Soret ultraviolet-visible (UV-vis) spectrum of ferric DGCR8, bis-thiolate sulfur (cysteinate, Cys(-)) heme iron coordination of DGCR8 heme iron was proposed. We have characterized DGCR8 heme ligation using the Δ276 DGCR8 variant and combined electron paramagnetic resonance (EPR), magnetic circular dichroism (MCD), electron nuclear double resonance, resonance Raman, and electronic absorption spectroscopy...
September 13, 2016: Biochemistry
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