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https://www.readbyqxmd.com/read/28709769/exploring-the-mitochondrial-microrna-import-pathway-through-polynucleotide-phosphorylase-pnpase
#1
Danielle L Shepherd, Quincy A Hathaway, Mark V Pinti, Cody E Nichols, Andrya J Durr, Shruthi Sreekumar, Kristen M Hughes, Seth M Stine, Ivan Martinez, John M Hollander
Cardiovascular disease is the primary cause of mortality for individuals with type 2 diabetes mellitus. During the diabetic condition, cardiovascular dysfunction can be partially attributed to molecular changes in the tissue, including alterations in microRNA (miRNA) interactions. MiRNAs have been reported in the mitochondrion and their presence may influence cellular bioenergetics, creating decrements in functional capacity. In this study, we examined the roles of Argonaute 2 (Ago2), a protein associated with cytosolic and mitochondrial miRNAs, and Polynucleotide Phosphorylase (PNPase), a protein found in the inner membrane space of the mitochondrion, to determine their role in mitochondrial miRNA import...
July 11, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28708135/regulation-of-plk1-through-competition-between-hnrnpk-mir-149-3p-and-mir-193b-5p
#2
Chang Hoon Shin, Hong Lee, Hye Ree Kim, Kyung Hee Choi, Je-Gun Joung, Hyeon Ho Kim
Polo-like kinase 1 (PLK1) is a critical regulator of cell cycle progression and apoptosis. However, its regulation remains poorly understood. In the present study, we investigated the molecular mechanism underlying the post-transcriptional regulation of PLK1. We observed that heterogeneous nuclear ribonucleoprotein K (hnRNPK) and PLK1 were positively associated in several different cancers and high expression levels of them correlated with poor prognosis in patients with cancer. Knockdown of hnRNPK resulted in reduced expression of PLK1, whereas conversely, PLK1 expression was increased in hnRNPK-overexpressing cells...
July 14, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28703801/lncrna-miat-functions-as-a-competing-endogenous-rna-to-upregulate-dapk2-by-sponging-mir-22-3p-in-diabetic-cardiomyopathy
#3
Xiang Zhou, Wei Zhang, Mengchao Jin, Jianchang Chen, Weiting Xu, Xiangqing Kong
We previously established a rat model of diabetic cardiomyopathy (DCM) and found that the expression of long non-coding RNA myocardial infarction-associated transcript (MIAT) was significantly upregulated. The present study was aimed to determine the pathologic role of MIAT in the development of DCM. MIAT knockdown was found to reduce cardiomyocyte apoptosis and improve left ventricular function in diabetic rats. High glucose could increase MIAT expression and induce apoptosis in cultured neonatal cardiomyocytes...
July 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28695996/downregulation-of-genes-coding-for-core-rnai-components-and-disease-resistance-proteins-via-corresponding-micrornas-might-be-correlated-with-successful-smv-infection-in-soybean
#4
Duran Bao, Oyunchuluun Ganbaatar, Xiuqi Cui, Ruonan Yu, Wenhua Bao, Bryce W Falk, Hada Wuriyanghan
Plants protect themselves from virus infections by several different defense mechanisms. RNA interference (RNAi) is one prominent antiviral mechanism, which requires the participation of AGO (Argonaute) and Dicer/DCL (Dicer-like) proteins. Effector-triggered immunity (ETI) is an antiviral mechanism mediated by resistance (R) genes, most of which encode NBS-LRR family proteins. MicroRNAs (miRNAs) play important regulatory roles in plants, including regulation of host defenses. SMV (Soybean mosaic virus) is the most common virus in soybean and here we identified dozens of SMV-responsive miRNAs by microarray analysis in a SMV-susceptible soybean line...
July 11, 2017: Molecular Plant Pathology
https://www.readbyqxmd.com/read/28683311/argonaute-utilization-for-mirna-silencing-is-determined-by-phosphorylation-dependent-recruitment-of-lim-domain-containing-proteins
#5
Katherine S Bridge, Kunal M Shah, Yigen Li, Daniel E Foxler, Sybil C K Wong, Duncan C Miller, Kathryn M Davidson, John G Foster, Ruth Rose, Michael R Hodgkinson, Paulo S Ribeiro, A Aziz Aboobaker, Kenta Yashiro, Xiaozhong Wang, Paul R Graves, Michael J Plevin, Dimitris Lagos, Tyson V Sharp
As core components of the microRNA-induced silencing complex (miRISC), Argonaute (AGO) proteins interact with TNRC6 proteins, recruiting other effectors of translational repression/mRNA destabilization. Here, we show that LIMD1 coordinates the assembly of an AGO-TNRC6 containing miRISC complex by binding both proteins simultaneously at distinct interfaces. Phosphorylation of AGO2 at Ser 387 by Akt3 induces LIMD1 binding, which in turn enables AGO2 to interact with TNRC6A and downstream effector DDX6. Conservation of this serine in AGO1 and 4 indicates this mechanism may be a fundamental requirement for AGO function and miRISC assembly...
July 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/28673815/autoantibodies-to-su-argonaute-2-in-japanese-patients-with-inflammatory-myopathy
#6
Mariko Ogawa-Momohara, Yoshinao Muro, Minoru Satoh, Masashi Akiyama
BACKGROUND: Anti-Su antibodies are found in 5-20% of cases of various systemic autoimmune rheumatic diseases and in 5-10% of dermatomyositis (DM)/polymyositis (PM) patients. In 2006, the 100kDa Su antigen was identified as argonaute2 (Ago2), and it was found to play a major role in RNA interference. However, immunoprecipitation (IP) remains the main method for detecting anti-Su and the clinical significance of the antibodies is uncertain. METHODS: Sera from patients with DM/PM (n=224) were screened by an ELISA that uses recombinant biotinylated Ago2 protein...
June 30, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28662698/mov10-suppresses-retroelements-and-regulates-neuronal-development-and-function-in-the-developing-brain
#7
Geena Skariah, Joseph Seimetz, Miles Norsworthy, Monica C Lannom, Phillip J Kenny, Mohamed Elrakhawy, Craig Forsthoefel, Jenny Drnevich, Auinash Kalsotra, Stephanie Ceman
BACKGROUND: Moloney leukemia virus 10 (Mov10) is an RNA helicase that mediates access of the RNA-induced silencing complex to messenger RNAs (mRNAs). Until now, its role as an RNA helicase and as a regulator of retrotransposons has been characterized exclusively in cell lines. We investigated the role of Mov10 in the mouse brain by examining its expression over development and attempting to create a Mov10 knockout mouse. Loss of both Mov10 copies led to early embryonic lethality. RESULTS: Mov10 was significantly elevated in postnatal murine brain, where it bound retroelement RNAs and mRNAs...
June 29, 2017: BMC Biology
https://www.readbyqxmd.com/read/28658280/reversible-perturbations-of-gene-regulation-after-genome-editing-in-drosophila-cells
#8
Stefan Kunzelmann, Klaus Förstemann
The prokaryotic phage defense CRISPR/cas-system has developed into a versatile toolbox for genome engineering and genetic studies in many organisms. While many efforts were spent on analyzing the consequences of off-target effects, only few studies addressed side-effects that occur due to the targeted manipulation of the genome. Here, we show that the CRISPR/cas9-mediated integration of an epitope tag in combination with a selection cassette can trigger an siRNA-mediated, epigenetic genome surveillance pathway in Drosophila melanogaster cells...
2017: PloS One
https://www.readbyqxmd.com/read/28645918/phosphorylation-of-argonaute-proteins-affects-mrna-binding-and-is-essential-for-microrna-guided-gene-silencing-in%C3%A2-vivo
#9
Miguel Quévillon Huberdeau, Daniela M Zeitler, Judith Hauptmann, Astrid Bruckmann, Lucile Fressigné, Johannes Danner, Sandra Piquet, Nicholas Strieder, Julia C Engelmann, Guillaume Jannot, Rainer Deutzmann, Martin J Simard, Gunter Meister
Argonaute proteins associate with microRNAs and are key components of gene silencing pathways. With such a pivotal role, these proteins represent ideal targets for regulatory post-translational modifications. Using quantitative mass spectrometry, we find that a C-terminal serine/threonine cluster is phosphorylated at five different residues in human and Caenorhabditis elegans In human, hyper-phosphorylation does not affect microRNA binding, localization, or cleavage activity of Ago2. However, mRNA binding is strongly affected...
July 14, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28639195/mirna-mediated-rnaa-by-targeting-enhancers
#10
Qingping Zou, Ying Liang, Huaibing Luo, Wenqiang Yu
MicroRNAs (miRNAs) are small noncoding RNAs that act as negative regulators of gene expression in the cytoplasm. Yet, emerging evidence has shown that miRNAs are also distributed in the nucleus, with its function largely undetermined. At the same time, while miRNAs and enhancers show obvious tissue specificity, the interaction between miRNAs and enhancers in gene regulation remains unknown. By screening miRNA databases, we have identified a subset of miRNAs, called nuclear activating miRNAs (NamiRNAs). As enhancer regulators, NamiRNAs are able to activate gene expression at the transcriptional level...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28639190/target-recognition-mechanism-and-specificity-of-rna-activation
#11
Huiqing Cao, Xing Meng, Xiaoxia Wang, Zicai Liang
Small activating RNA (saRNA)-mediated gene activation has opened a new avenue for upregulating the expression of target genes by promoting endogenous transcription, a phenomenon known as RNA activation (RNAa). RNAa is distinct from the established RNAi mechanistic framework, although AGO2 is required by both. The precise mechanism of RNAa is currently disputable and has become a bottleneck in the development of this new technology. saRNA may achieve activation of target genes by directly binding to DNA targets in promoter, or interacting with antisense transcripts transcribed from overlapping promoter sequences, or by silencing other genes...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28634830/the-microrna-effector-rna-induced-silencing-complex-in-hidradenitis-suppurativa-a-significant-dysregulation-within-active-inflammatory-lesions
#12
S Hessam, M Sand, M Skrygan, Falk G Bechara
Recently, we could show that the expression levels of the key regulators of the microRNA (miRNA) maturation and transport were dysregulated in inflamed hidradenitis suppurativa (HS) tissue (Heyam et al. in Wiley Interdiscip Rev RNA 6:271-289, 2015). The RNA-induced silencing complex (RISC) is the central element of the miRNA pathway and regulates miRNA formation and function. We investigated the expression of the RISC components, namely transactivation-responsive RNA-binding protein-1 (TRBP1), TRBP2, protein activator (PACT) of the interferon-induced protein kinase R, Argonaute RISC Catalytic Component-1 (AGO1) and Component-2 (AGO2), metadherin, and staphylococcal nuclease and Tudor domain-containing-1 (SND1) in inflamed HS tissue compared to healthy and psoriatic controls by real-time reverse transcription polymerase chain reaction...
June 20, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28629895/tumour-suppressor-micrornas-contribute-to-the-regulation-of-pd-l1-expression-in-malignant-pleural-mesothelioma
#13
Steven C Kao, Yuen Yee Cheng, Marissa Williams, Michaela B Kirschner, Jason Madore, Trina Lum, Kadir H Sarun, Anthony Linton, Brian McCaughan, Sonja Klebe, Nico van Zandwijk, Richard A Scolyer, Michael J Boyer, Wendy A Cooper, Glen Reid
INTRODUCTION: The upregulation of PD-L1 is found in many cancers and contributes to the evasion of the host's immune defence. In malignant pleural mesothelioma (MPM), PD-L1 expression is associated with non-epithelioid histological subtype and poor prognosis, but the pathways involved in the control of PD-L1 expression in MPM are poorly understood. To address one possible means of PD-L1 regulation we investigated the relationship between dysregulated microRNA levels and PD-L1 expression...
June 16, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28605404/recent-computational-developments-on-clip-seq-data-analysis-and-microrna-targeting-implications
#14
Silvia Bottini, David Pratella, Valerie Grandjean, Emanuela Repetto, Michele Trabucchi
Cross-Linking Immunoprecipitation associated to high-throughput sequencing (CLIP-seq) is a technique used to identify RNA directly bound to RNA-binding proteins across the entire transcriptome in cell or tissue samples. Recent technological and computational advances permit the analysis of many CLIP-seq samples simultaneously, allowing us to reveal the comprehensive network of RNA-protein interaction and to integrate it to other genome-wide analyses. Therefore, the design and quality management of the CLIP-seq analyses are of critical importance to extract clean and biological meaningful information from CLIP-seq experiments...
June 12, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/28591738/ago2-involves-the-malignant-phenotypes-and-fak-pi3k-akt-signaling-pathway-in-hypopharyngeal-derived-fadu-cells
#15
Yanhui Zhang, Baoxin Wang, Xinwei Chen, Weidong Li, Pin Dong
Argonaute 2 (AGO2) protein is usually overexpressed in various head and neck squamous cell carcinoma. However, the precise molecular mechanisms of AGO2 in hypopharyngeal cancer have not yet been clearly understood. Here we found the AGO2 expression in hypopharyngeal cancer tissues were generally higher comparing with that of the corresponding adjacent noncancerous epithelium tissues, and these were associated with the more aggressive clinicopathologic features and the poor clinical outcomes. Stable knockdown of AGO2 protein retarded cell proliferation, migration, invasion, arrested cell cycle and induced apoptosis...
May 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28589097/ago2-negatively-regulates-type-i-interferon-signaling-pathway-by-competition-binding-irf3-with-cbp-p300
#16
Shengyu Wang, Xin Sun, Chenyang Yi, Dan Zhang, Xian Lin, Xiaomei Sun, Huanchun Chen, Meilin Jin
Viral infection triggers a series of signaling cascades and host innate immune responses, including interferon (IFN) production, which depends on coordinated activity of multiple transcription factors. IFN regulatory factor 3 (IRF3) and transcriptional coactivator CREB binding protein (CBP) and/or p300 are core factors that participate in transcriptional complex formation in the nucleus. In general, cells balance the production of IFNs through suppressive and stimulative mechanisms, but viral infections can disrupt such equilibrium...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28585547/split-bioid-a-conditional-proteomics-approach-to-monitor-the-composition-of-spatiotemporally-defined-protein-complexes
#17
Isabel Myriam Schopp, Cinthia Claudia Amaya Ramirez, Jerneja Debeljak, Elisa Kreibich, Merle Skribbe, Klemens Wild, Julien Béthune
Understanding the function of the thousands of cellular proteins is a central question in molecular cell biology. As proteins are typically part of multiple dynamic and often overlapping macromolecular complexes exerting distinct functions, the identification of protein-protein interactions (PPI) and their assignment to specific complexes is a crucial but challenging task. We present a protein fragments complementation assay integrated with the proximity-dependent biotinylation technique BioID. Activated on the interaction of two proteins, split-BioID is a conditional proteomics approach that allows in a single and simple assay to both experimentally validate binary PPI and to unbiasedly identify additional interacting factors...
June 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28569591/influence-of-the-loop-size-and-nucleotide-composition-on-agoshrna-biogenesis-and-activity
#18
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/28559278/the-p90-ribosomal-s6-kinase-ubr5-pathway-controls-toll-like-receptor-signaling-via-mirna-induced-translational-inhibition-of-tnf-receptor-associated-factor-3
#19
Jin Hwa Cho, Sung Ah Kim, Yeon-Soo Seo, Sung Goo Park, Byoung Chul Park, Jeong-Hoon Kim, Sunhong Kim
MicroRNAs (miRNAs) are small, noncoding RNAs that post-transcriptionally regulate gene expression. For example, miRNAs repress gene expression by recruiting the miRNA-induced silencing complex (miRISC), a ribonucleoprotein complex that contains miRNA-engaged Argonaute (Ago) and the scaffold protein GW182. Recently, ubiquitin protein ligase E3 component N-recognin 5 (UBR5) has been identified as a component of miRISC. UBR5 directly interacts with GW182 proteins and participates in miRNA silencing by recruiting downstream effectors, such as the translation regulator DEAD-box helicase 6 (DDX6) and transducer of ERBB2...
May 30, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28557556/regulating-the-regulators-in-attention-deficit-hyperactivity-disorder-a-genetic-association-study-of-microrna-biogenesis-pathways
#20
Umit Karakas, Ozlem Izci Ay, Mustafa Ertan Ay, Wei Wang, Mehmet Ali Sungur, Kenan Çevik, Gurbet Dogru, Mehmet Emin Erdal
Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent complex psychiatric disorders in children as well as adults. ADHD impacts not only the affected individuals but also their families and social and professional networks. The clinical and diagnostic criteria for ADHD remain imprecise, in part, due to lack of robust biomarkers. ADHD comprises multiple subsets of diseases that present a shared set of downstream clinical findings, while displaying extensive molecular heterogeneity. This calls for innovation in diagnostic strategies that can help establish an ADHD diagnosis unequivocally as well as guiding precision medicine in this common mental health disorder...
June 2017: Omics: a Journal of Integrative Biology
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