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https://www.readbyqxmd.com/read/28634830/the-microrna-effector-rna-induced-silencing-complex-in-hidradenitis-suppurativa-a-significant-dysregulation-within-active-inflammatory-lesions
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/28553938/the-mbnl3-splicing-factor-promotes-hepatocellular-carcinoma-by-increasing-pxn-expression-through-the-alternative-splicing-of-lncrna-pxn-as1
#10
Ji-Hang Yuan, Xiao-Ning Liu, Tian-Tian Wang, Wei Pan, Qi-Fei Tao, Wei-Ping Zhou, Fang Wang, Shu-Han Sun
Understanding the roles of splicing factors and splicing events during tumorigenesis would open new avenues for targeted therapies. Here we identify an oncofetal splicing factor, MBNL3, which promotes tumorigenesis and indicates poor prognosis of hepatocellular carcinoma patients. MBNL3 knockdown almost completely abolishes hepatocellular carcinoma tumorigenesis. Transcriptomic analysis revealed that MBNL3 induces lncRNA-PXN-AS1 exon 4 inclusion. The transcript lacking exon 4 binds to coding sequences of PXN mRNA, causes dissociation of translation elongation factors from PXN mRNA, and thereby inhibits PXN mRNA translation...
May 29, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28553929/silencing-of-hiv-1-by-agoshrna-molecules
#11
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/28542329/novel-agoshrna-molecules-for-silencing-of-the-ccr5-co-receptor-for-hiv-1-infection
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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