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Pesquisa : D08.811.913.696.445.735.270.775 [Categoria DeCS]
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[PMID]:28743884
[Au] Autor:Gouge J; Guthertz N; Kramm K; Dergai O; Abascal-Palacios G; Satia K; Cousin P; Hernandez N; Grohmann D; Vannini A
[Ad] Endereço:The Institute of Cancer Research, London, SW7 3RP, UK.
[Ti] Título:Molecular mechanisms of Bdp1 in TFIIIB assembly and RNA polymerase III transcription initiation.
[So] Source:Nat Commun;8(1):130, 2017 07 25.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Initiation of gene transcription by RNA polymerase (Pol) III requires the activity of TFIIIB, a complex formed by Brf1 (or Brf2), TBP (TATA-binding protein), and Bdp1. TFIIIB is required for recruitment of Pol III and to promote the transition from a closed to an open Pol III pre-initiation complex, a process dependent on the activity of the Bdp1 subunit. Here, we present a crystal structure of a Brf2-TBP-Bdp1 complex bound to DNA at 2.7 Å resolution, integrated with single-molecule FRET analysis and in vitro biochemical assays. Our study provides a structural insight on how Bdp1 is assembled into TFIIIB complexes, reveals structural and functional similarities between Bdp1 and Pol II factors TFIIA and TFIIF, and unravels essential interactions with DNA and with the upstream factor SNAPc. Furthermore, our data support the idea of a concerted mechanism involving TFIIIB and RNA polymerase III subunits for the closed to open pre-initiation complex transition.Transcription initiation by RNA polymerase III requires TFIIIB, a complex formed by Brf1/Brf2, TBP and Bdp1. Here, the authors describe the crystal structure of a Brf2-TBP-Bdp1 complex bound to a DNA promoter and characterize the role of Bdp1 in TFIIIB assembly and pre-initiation complex formation.
[Mh] Termos MeSH primário: RNA Polimerase III/metabolismo
Fator de Transcrição TFIIIB/metabolismo
Iniciação da Transcrição Genética
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Cristalografia por Raios X
DNA/química
DNA/genética
DNA/metabolismo
Seres Humanos
Modelos Moleculares
Conformação de Ácido Nucleico
Regiões Promotoras Genéticas/genética
Ligação Proteica
Domínios Proteicos
Homologia de Sequência de Aminoácidos
Proteína de Ligação a TATA-Box/química
Proteína de Ligação a TATA-Box/genética
Proteína de Ligação a TATA-Box/metabolismo
Fator de Transcrição TFIIIB/química
Fator de Transcrição TFIIIB/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (BDP1 protein, human); 0 (BRF2 protein, human); 0 (TATA-Box Binding Protein); 0 (TBP protein, human); 0 (Transcription Factor TFIIIB); 9007-49-2 (DNA); EC 2.7.7.6 (RNA Polymerase III)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171128
[Lr] Data última revisão:
171128
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170727
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-00126-1


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[PMID]:28973449
[Au] Autor:Burke JM; Kincaid RP; Aloisio F; Welch N; Sullivan CS
[Ad] Endereço:The University of Texas at Austin, Institute for Cellular and Molecular Biology, Center for Synthetic and Systems Biology, Center for Infectious Disease and Department Molecular Biosciences, 1 University Station A5000, Austin, TX 78712-0162, USA.
[Ti] Título:Expression of short hairpin RNAs using the compact architecture of retroviral microRNA genes.
[So] Source:Nucleic Acids Res;45(17):e154, 2017 Sep 29.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Short hairpin RNAs (shRNAs) are effective in generating stable repression of gene expression. RNA polymerase III (RNAP III) type III promoters (U6 or H1) are typically used to drive shRNA expression. While useful for some knockdown applications, the robust expression of U6/H1-driven shRNAs can induce toxicity and generate heterogeneous small RNAs with undesirable off-target effects. Additionally, typical U6/H1 promoters encompass the majority of the ∼270 base pairs (bp) of vector space required for shRNA expression. This can limit the efficacy and/or number of delivery vector options, particularly when delivery of multiple gene/shRNA combinations is required. Here, we develop a compact shRNA (cshRNA) expression system based on retroviral microRNA (miRNA) gene architecture that uses RNAP III type II promoters. We demonstrate that cshRNAs coded from as little as 100 bps of total coding space can precisely generate small interfering RNAs (siRNAs) that are active in the RNA-induced silencing complex (RISC). We provide an algorithm with a user-friendly interface to design cshRNAs for desired target genes. This cshRNA expression system reduces the coding space required for shRNA expression by >2-fold as compared to the typical U6/H1 promoters, which may facilitate therapeutic RNAi applications where delivery vector space is limiting.
[Mh] Termos MeSH primário: Marcação de Genes/métodos
Vírus da Leucemia Bovina/genética
MicroRNAs/genética
RNA Polimerase III/genética
RNA Interferente Pequeno/genética
RNA Viral/genética
[Mh] Termos MeSH secundário: Algoritmos
Pareamento de Bases
Sequência de Bases
Regulação da Expressão Gênica
Inativação Gênica
Genes Reporter
Vetores Genéticos
Células HEK293
Seres Humanos
Vírus da Leucemia Bovina/metabolismo
Luciferases/genética
Luciferases/metabolismo
MicroRNAs/metabolismo
Regiões Promotoras Genéticas
RNA Polimerase III/metabolismo
RNA Interferente Pequeno/metabolismo
RNA Viral/metabolismo
Complexo de Inativação Induzido por RNA/genética
Complexo de Inativação Induzido por RNA/metabolismo
Análise de Sequência de RNA
Interface Usuário-Computador
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (MicroRNAs); 0 (RNA, Small Interfering); 0 (RNA, Viral); 0 (RNA-Induced Silencing Complex); EC 1.13.12.- (Luciferases); EC 2.7.7.6 (RNA Polymerase III)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171004
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx653


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[PMID]:28961268
[Au] Autor:Adamczyk M; Szatkowska R
[Ad] Endereço:Institute of Biotechnology, Faculty of Chemistry, Warsaw University of Technology, Warsaw, Poland.
[Ti] Título:Low RNA Polymerase III activity results in up regulation of HXT2 glucose transporter independently of glucose signaling and despite changing environment.
[So] Source:PLoS One;12(9):e0185516, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Saccharomyces cerevisiae responds to glucose availability in the environment, inducing the expression of the low-affinity transporters and high-affinity transporters in a concentration dependent manner. This cellular decision making is controlled through finely tuned communication between multiple glucose sensing pathways including the Snf1-Mig1, Snf3/Rgt2-Rgt1 (SRR) and cAMP-PKA pathways. RESULTS: We demonstrate the first evidence that RNA Polymerase III (RNAP III) activity affects the expression of the glucose transporter HXT2 (RNA Polymerase II dependent-RNAP II) at the level of transcription. Down-regulation of RNAP III activity in an rpc128-1007 mutant results in a significant increase in HXT2 mRNA, which is considered to respond only to low extracellular glucose concentrations. HXT2 expression is induced in the mutant regardless of the growth conditions either at high glucose concentration or in the presence of a non-fermentable carbon source such as glycerol. Using chromatin immunoprecipitation (ChIP), we found an increased association of Rgt1 and Tup1 transcription factors with the highly activated HXT2 promoter in the rpc128-1007 strain. Furthermore, by measuring cellular abundance of Mth1 corepressor, we found that in rpc128-1007, HXT2 gene expression was independent from Snf3/Rgt2-Rgt1 (SRR) signaling. The Snf1 protein kinase complex, which needs to be active for the release from glucose repression, also did not appear perturbed in the mutated strain. CONCLUSIONS/SIGNIFICANCE: These findings suggest that the general activity of RNAP III can indirectly affect the RNAP II transcriptional machinery on the HXT2 promoter when cellular perception transduced via the major signaling pathways, broadly recognized as on/off switch essential to either positive or negative HXT gene regulation, remain entirely intact. Further, Rgt1/Ssn6-Tup1 complex, which has a dual function in gene transcription as a repressor-activator complex, contributes to HXT2 transcriptional activation.
[Mh] Termos MeSH primário: Proteínas Facilitadoras de Transporte de Glucose/metabolismo
Glucose/metabolismo
RNA Polimerase III/metabolismo
Proteínas de Saccharomyces cerevisiae/metabolismo
Transdução de Sinais
Regulação para Cima
[Mh] Termos MeSH secundário: Western Blotting
Proteínas Facilitadoras de Transporte de Glucose/genética
Imunoprecipitação
Mutação
Reação em Cadeia da Polimerase em Tempo Real
Saccharomyces cerevisiae/metabolismo
Proteínas de Saccharomyces cerevisiae/genética
Transcrição Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Glucose Transport Proteins, Facilitative); 0 (HXT2 protein, S cerevisiae); 0 (Saccharomyces cerevisiae Proteins); EC 2.7.7.6 (RNA Polymerase III); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171103
[Lr] Data última revisão:
171103
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170930
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0185516


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[PMID]:28945233
[Au] Autor:Song W; Filonov GS; Kim H; Hirsch M; Li X; Moon JD; Jaffrey SR
[Ad] Endereço:Department of Pharmacology, Weill Medical College, Cornell University, New York, New York, USA.
[Ti] Título:Imaging RNA polymerase III transcription using a photostable RNA-fluorophore complex.
[So] Source:Nat Chem Biol;13(11):1187-1194, 2017 Nov.
[Is] ISSN:1552-4469
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Quantitative measurement of transcription rates in live cells is important for revealing mechanisms of transcriptional regulation. This is particularly challenging when measuring the activity of RNA polymerase III (Pol III), which transcribes growth-promoting small RNAs. To address this issue, we developed Corn, a genetically encoded fluorescent RNA reporter suitable for quantifying RNA transcription in cells. Corn binds and induces fluorescence of 3,5-difluoro-4-hydroxybenzylidene-imidazolinone-2-oxime, which resembles the fluorophore found in red fluorescent protein (RFP). Notably, Corn shows high photostability, enabling quantitative fluorescence imaging of mTOR-dependent Pol III transcription. We found that, unlike actinomycin D, mTOR inhibitors resulted in heterogeneous transcription suppression in individual cells. Quantitative imaging of Corn-tagged Pol III transcript levels revealed distinct Pol III transcription 'trajectories' elicited by mTOR inhibition. Together, these studies provide an approach for quantitative measurement of Pol III transcription by direct imaging of Pol III transcripts containing a photostable RNA-fluorophore complex.
[Mh] Termos MeSH primário: Aptâmeros de Nucleotídeos/genética
Inativação Luminosa Assistida por Cromóforo
Corantes Fluorescentes/metabolismo
Imagem Óptica/métodos
RNA Polimerase III/análise
Transcrição Genética
[Mh] Termos MeSH secundário: Aptâmeros de Nucleotídeos/metabolismo
Pareamento de Bases
Sequência de Bases
Regulação da Expressão Gênica
Células HEK293
Seres Humanos
Proteínas Luminescentes/metabolismo
Conformação de Ácido Nucleico
RNA Polimerase III/genética
Sirolimo/análogos & derivados
Sirolimo/farmacologia
Serina-Treonina Quinases TOR/antagonistas & inibidores
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aptamers, Nucleotide); 0 (Fluorescent Dyes); 0 (Luminescent Proteins); 0 (red fluorescent protein); 624KN6GM2T (temsirolimus); EC 2.7.1.1 (MTOR protein, human); EC 2.7.1.1 (TOR Serine-Threonine Kinases); EC 2.7.7.6 (RNA Polymerase III); W36ZG6FT64 (Sirolimus)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171111
[Lr] Data última revisão:
171111
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170926
[St] Status:MEDLINE
[do] DOI:10.1038/nchembio.2477


  5 / 1660 MEDLINE  
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[PMID]:28890398
[Au] Autor:Huang Y; Wang Y; Zeng B; Liu Z; Xu X; Meng Q; Huang Y; Yang G; Vasseur L; Gurr GM; You M
[Ad] Endereço:State Key Laboratory for Ecological Pest Control of Fujian/Taiwan Crops and College of Life Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China; Institute of Applied Ecology, Fujian Agriculture and Forestry University, Fuzhou 350002, China; Fujian-Taiwan Joint Innovation Centre
[Ti] Título:Functional characterization of Pol III U6 promoters for gene knockdown and knockout in Plutella xylostella.
[So] Source:Insect Biochem Mol Biol;89:71-78, 2017 Oct.
[Is] ISSN:1879-0240
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:RNA polymerase type III (Pol-III) promoters such as U6 are commonly used to express small RNAs, including short hairpin RNAs (shRNAs) and single guide RNAs (sgRNAs). Functional U6 promoters are widely used in CRISPR systems, and their characterization can facilitate genome editing of non-model organisms. In the present study, six U6 small nuclear RNA (snRNA) promoters containing two conserved elements of a proximal sequence element (PSEA) and a TATA box, were identified and characterized in the diamondback moth (Plutella xylostella) genome. Relative efficiency of the U6 promoters to express shRNA induced EGFP knockdown was tested in a P. xylostella cell line, revealing that the PxU6:3 promoter had the strongest expression effect. Further work with the PxU6:3 promoter showed its efficacy in EGFP knockout using CRISPR/Cas9 system in the cells. The expression plasmids with versatile Pxabd-A gene specific sgRNA driven by the PxU6:3 promoter, combined with Cas9 mRNA, could induce mutagenesis at specific genomic loci in vivo. The phenotypes induced by sgRNA expression plasmids were similar to those done in vitro transcription sgRNAs. A plasmid with two tandem arranged PxU6:3:sgRNA expression cassettes targeting Pxabd-A loci was generated, which caused a 28,856 bp fragment deletion, suggesting that the multi-sgRNA expression plasmid can be used for multi-targeting. Our work indicates that U6 snRNA promoters can be used for functional studies of genes with the approach of reverse genetics in P. xylostella. These essential promoters also provide valuable potential for CRISPR-derived gene drive as a tactic for population control in this globally significant pest.
[Mh] Termos MeSH primário: Sistemas CRISPR-Cas
Mariposas/genética
Regiões Promotoras Genéticas
RNA Polimerase III/genética
[Mh] Termos MeSH secundário: Animais
Sequência de Bases
Feminino
Técnicas de Silenciamento de Genes
Técnicas de Inativação de Genes
Genoma de Inseto
Masculino
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 2.7.7.6 (RNA Polymerase III)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170912
[St] Status:MEDLINE


  6 / 1660 MEDLINE  
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[PMID]:28846843
[Au] Autor:Appling FD; Schneider DA; Lucius AL
[Ad] Endereço:Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham , Birmingham, Alabama 35294, United States.
[Ti] Título:Multisubunit RNA Polymerase Cleavage Factors Modulate the Kinetics and Energetics of Nucleotide Incorporation: An RNA Polymerase I Case Study.
[So] Source:Biochemistry;56(42):5654-5662, 2017 Oct 24.
[Is] ISSN:1520-4995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:All cellular RNA polymerases are influenced by protein factors that stimulate RNA polymerase-catalyzed cleavage of the nascent RNA. Despite divergence in amino acid sequence, these so-called "cleavage factors" appear to share a common mechanism of action. Cleavage factors associate with the polymerase through a conserved structural element of the polymerase known as the secondary channel or pore. This mode of association enables the cleavage factor to reach through the secondary channel into the polymerase active site to reorient the active site divalent metal ions. This reorientation converts the polymerase active site into a nuclease active site. Interestingly, eukaryotic RNA polymerases I and III (Pols I and III, respectively) have incorporated their cleavage factors as bona fide subunits known as A12.2 and C11, respectively. Although it is clear that A12.2 and C11 dramatically stimulate the polymerase's cleavage activity, it is not known if or how these subunits affect the polymerization mechanism. In this work we have used transient-state kinetic techniques to characterize a Pol I isoform lacking A12.2. Our data clearly demonstrate that the A12.2 subunit profoundly affects the kinetics and energetics of the elementary steps of Pol I-catalyzed nucleotide incorporation. Given the high degree of conservation between polymerase-cleavage factor interactions, these data indicate that cleavage factor-modulated nucleotide incorporation mechanisms may be common to all cellular RNA polymerases.
[Mh] Termos MeSH primário: Nucleotídeos/química
RNA Polimerase I/química
Proteínas de Saccharomyces cerevisiae/química
Saccharomyces cerevisiae/enzimologia
Fatores de Poliadenilação e Clivagem de mRNA/química
[Mh] Termos MeSH secundário: Cinética
Nucleotídeos/metabolismo
RNA Polimerase I/metabolismo
RNA Polimerase III/química
RNA Polimerase III/metabolismo
Proteínas de Saccharomyces cerevisiae/metabolismo
Fatores de Poliadenilação e Clivagem de mRNA/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Nucleotides); 0 (Saccharomyces cerevisiae Proteins); 0 (mRNA Cleavage and Polyadenylation Factors); EC 2.7.7.6 (RNA Polymerase I); EC 2.7.7.6 (RNA Polymerase III)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171027
[Lr] Data última revisão:
171027
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170829
[St] Status:MEDLINE
[do] DOI:10.1021/acs.biochem.7b00370


  7 / 1660 MEDLINE  
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[PMID]:28783042
[Au] Autor:Ogunjimi B; Zhang SY; Sørensen KB; Skipper KA; Carter-Timofte M; Kerner G; Luecke S; Prabakaran T; Cai Y; Meester J; Bartholomeus E; Bolar NA; Vandeweyer G; Claes C; Sillis Y; Lorenzo L; Fiorenza RA; Boucherit S; Dielman C; Heynderickx S; Elias G; Kurotova A; Auwera AV; Verstraete L; Lagae L; Verhelst H; Jansen A; Ramet J; Suls A; Smits E; Ceulemans B; Van Laer L; Plat Wilson G; Kreth J; Picard C; Von Bernuth H; Fluss J; Chabrier S; Abel L; Mortier G; Fribourg S; Mikkelsen JG; Casanova JL; Paludan SR; Mogensen TH
[Ad] Endereço:Centre for Health Economics Research & Modeling Infectious Diseases, Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.
[Ti] Título:Inborn errors in RNA polymerase III underlie severe varicella zoster virus infections.
[So] Source:J Clin Invest;127(9):3543-3556, 2017 Sep 01.
[Is] ISSN:1558-8238
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Varicella zoster virus (VZV) typically causes chickenpox upon primary infection. In rare cases, VZV can give rise to life-threatening disease in otherwise healthy people, but the immunological basis for this remains unexplained. We report 4 cases of acute severe VZV infection affecting the central nervous system or the lungs in unrelated, otherwise healthy children who are heterozygous for rare missense mutations in POLR3A (one patient), POLR3C (one patient), or both (two patients). POLR3A and POLR3C encode subunits of RNA polymerase III. Leukocytes from all 4 patients tested exhibited poor IFN induction in response to synthetic or VZV-derived DNA. Moreover, leukocytes from 3 of the patients displayed defective IFN production upon VZV infection and reduced control of VZV replication. These phenotypes were rescued by transduction with relevant WT alleles. This work demonstrates that monogenic or digenic POLR3A and POLR3C deficiencies confer increased susceptibility to severe VZV disease in otherwise healthy children, providing evidence for an essential role of a DNA sensor in human immunity.
[Mh] Termos MeSH primário: Varicela/genética
Herpes Zoster/genética
Mutação
RNA Polimerase III/genética
RNA Polimerase III/metabolismo
[Mh] Termos MeSH secundário: Alelos
Animais
Criança
Análise Mutacional de DNA
Regulação Enzimológica da Expressão Gênica
Células HEK293
Herpesvirus Humano 3
Heterozigoto
Seres Humanos
Leucócitos/metabolismo
Camundongos
Mutação de Sentido Incorreto
Fenótipo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 2.7.7.6 (RNA Polymerase III)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170808
[St] Status:MEDLINE


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[PMID]:28729413
[Au] Autor:Finlay-Schultz J; Gillen AE; Brechbuhl HM; Ivie JJ; Matthews SB; Jacobsen BM; Bentley DL; Kabos P; Sartorius CA
[Ad] Endereço:Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, Colorado. Jessica.Finlay-Schultz@ucdenver.edu Carol.Sartorius@ucdenver.edu.
[Ti] Título:Breast Cancer Suppression by Progesterone Receptors Is Mediated by Their Modulation of Estrogen Receptors and RNA Polymerase III.
[So] Source:Cancer Res;77(18):4934-4946, 2017 Sep 15.
[Is] ISSN:1538-7445
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Greater than 50% of estrogen receptor (ER)-positive breast cancers coexpress the progesterone receptor (PR), which can directly and globally modify ER action to attenuate tumor growth. However, whether this attenuation is mediated only through PR-ER interaction remains unknown. To address this question, we assessed tumor growth in ER/PR-positive patient-derived xenograft models of breast cancer, where both natural and synthetic progestins were found to antagonize the mitogenic effects of estrogens. Probing the genome-wide mechanisms by which this occurs, we documented that chronic progestin treatment blunted ER-mediated gene expression up to 2-fold at the level of mRNA transcripts. Unexpectedly, <25% of all ER DNA binding events were affected by the same treatment. The PR cistrome displayed a bimodal distribution. In one group, >50% of PR binding sites were co-occupied by ER, with a propensity for both receptors to coordinately gain or lose binding in the presence of progesterone. In the second group, PR but not ER was associated with a large fraction of RNA polymerase III-transcribed tRNA genes, independent of hormone treatment. Notably, we discovered that PR physically associated with the Pol III holoenzyme. Select pre-tRNAs and mature tRNAs with PR and POLR3A colocalized at their promoters were relatively decreased in estrogen + progestin-treated tumors. Our results illuminate how PR may indirectly impede ER action by reducing the bioavailability of translational molecules needed for tumor growth. .
[Mh] Termos MeSH primário: Neoplasias da Mama/metabolismo
Neoplasias da Mama/patologia
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Progestinas/farmacologia
RNA Polimerase III/metabolismo
Receptores Estrogênicos/metabolismo
Receptores de Progesterona/metabolismo
[Mh] Termos MeSH secundário: Adulto
Animais
Apoptose/efeitos dos fármacos
Biomarcadores Tumorais/metabolismo
Neoplasias da Mama/tratamento farmacológico
Proliferação Celular/efeitos dos fármacos
Estrogênios/farmacologia
Feminino
Perfilação da Expressão Gênica
Seres Humanos
Metástase Linfática
Camundongos
Camundongos Endogâmicos NOD
Camundongos SCID
Transdução de Sinais/efeitos dos fármacos
Células Tumorais Cultivadas
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (Estrogens); 0 (Progestins); 0 (Receptors, Estrogen); 0 (Receptors, Progesterone); EC 2.7.7.6 (RNA Polymerase III)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170722
[St] Status:MEDLINE
[do] DOI:10.1158/0008-5472.CAN-16-3541


  9 / 1660 MEDLINE  
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[PMID]:28709002
[Au] Autor:Nabet BY; Qiu Y; Shabason JE; Wu TJ; Yoon T; Kim BC; Benci JL; DeMichele AM; Tchou J; Marcotrigiano J; Minn AJ
[Ad] Endereço:Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
[Ti] Título:Exosome RNA Unshielding Couples Stromal Activation to Pattern Recognition Receptor Signaling in Cancer.
[So] Source:Cell;170(2):352-366.e13, 2017 Jul 13.
[Is] ISSN:1097-4172
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Interactions between stromal fibroblasts and cancer cells generate signals for cancer progression, therapy resistance, and inflammatory responses. Although endogenous RNAs acting as damage-associated molecular patterns (DAMPs) for pattern recognition receptors (PRRs) may represent one such signal, these RNAs must remain unrecognized under non-pathological conditions. We show that triggering of stromal NOTCH-MYC by breast cancer cells results in a POL3-driven increase in RN7SL1, an endogenous RNA normally shielded by RNA binding proteins SRP9/14. This increase in RN7SL1 alters its stoichiometry with SRP9/14 and generates unshielded RN7SL1 in stromal exosomes. After exosome transfer to immune cells, unshielded RN7SL1 drives an inflammatory response. Upon transfer to breast cancer cells, unshielded RN7SL1 activates the PRR RIG-I to enhance tumor growth, metastasis, and therapy resistance. Corroborated by evidence from patient tumors and blood, these results demonstrate that regulation of RNA unshielding couples stromal activation with deployment of RNA DAMPs that promote aggressive features of cancer. VIDEO ABSTRACT.
[Mh] Termos MeSH primário: Neoplasias da Mama/patologia
Exossomos/patologia
RNA não Traduzido/metabolismo
Células Estromais/patologia
Microambiente Tumoral
[Mh] Termos MeSH secundário: Neoplasias da Mama/metabolismo
Proteína DEAD-box 58/metabolismo
Exossomos/metabolismo
Seres Humanos
Fatores Reguladores de Interferon/metabolismo
Células MCF-7
Metástase Neoplásica
RNA Polimerase III/genética
RNA Polimerase III/metabolismo
Receptores de Reconhecimento de Padrão/metabolismo
Partícula de Reconhecimento de Sinal/metabolismo
Células Estromais/metabolismo
Viroses/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Interferon Regulatory Factors); 0 (RNA, Untranslated); 0 (Receptors, Pattern Recognition); 0 (SRP14 protein, human); 0 (SRP9 protein, human); 0 (Signal Recognition Particle); EC 2.7.7.6 (RNA Polymerase III); EC 3.6.1.- (DDX58 protein, human); EC 3.6.4.13 (DEAD Box Protein 58)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170929
[Lr] Data última revisão:
170929
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170715
[St] Status:MEDLINE


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[PMID]:28502960
[Au] Autor:Kuwana M
[Ad] Endereço:Department of Allergy and Rheumatology, Nippon Medical School.
[Ti] Título:Circulating Anti-Nuclear Antibodies in Systemic Sclerosis: Utility in Diagnosis and Disease Subsetting.
[So] Source:J Nippon Med Sch;84(2):56-63, 2017.
[Is] ISSN:1347-3409
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:The presence of circulating anti-nuclear antibodies (ANAs) is a hallmark of immune dysregulation in patients with systemic sclerosis (SSc). Currently, a variety of SSc-specific ANAs, including anticentromere, anti-topoisomerase I, and anti-RNA polymerase III antibodies, have been well characterized, and their commercial kits are available worldwide. Since these autoantibodies are specifically detected in SSc patients and are associated with unique sets of disease manifestations, they are widely used in routine clinical practice for diagnosis, clinical subgrouping, and prediction of future organ involvements and prognosis. In addition, SSc-specific ANAs are also useful in predicting future development of SSc in patients with Raynaud's phenomenon without any scleroderma skin changes, because their production often precedes onset of SSc symptoms. Application of circulating SSc-specific ANA measurement to clinical practice has greatly improved patient care, but utility of the autoantibody testing could be maximized by combining other clinical information, such as degree and extent of skin thickness and disease duration.
[Mh] Termos MeSH primário: Anticorpos Antinucleares/sangue
Escleroderma Sistêmico/diagnóstico
[Mh] Termos MeSH secundário: Anticorpos Antinucleares/classificação
Biomarcadores/sangue
DNA Topoisomerases Tipo I/imunologia
Seres Humanos
RNA Polimerase III/imunologia
Kit de Reagentes para Diagnóstico
Escleroderma Sistêmico/classificação
Escleroderma Sistêmico/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antibodies, Antinuclear); 0 (Biomarkers); 0 (Reagent Kits, Diagnostic); 0 (anticentromere antibody); EC 2.7.7.6 (RNA Polymerase III); EC 5.99.1.2 (DNA Topoisomerases, Type I)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170928
[Lr] Data última revisão:
170928
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170516
[St] Status:MEDLINE
[do] DOI:10.1272/jnms.84.56



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