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  1 / 1817 MEDLINE  
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[PMID]:28934498
[Au] Autor:Kim SW; Taggart AJ; Heintzelman C; Cygan KJ; Hull CG; Wang J; Shrestha B; Fairbrother WG
[Ad] Endereço:Department of Molecular and Cellular Biology, Brown University, Providence, RI 02903, USA.
[Ti] Título:Widespread intra-dependencies in the removal of introns from human transcripts.
[So] Source:Nucleic Acids Res;45(16):9503-9513, 2017 Sep 19.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Research into the problem of splice site selection has followed a reductionist approach focused on how individual splice sites are recognized. Early applications of information theory uncovered an inconsistency. Human splice signals do not contain enough information to explain the observed fidelity of splicing. Here, we conclude that introns do not necessarily contain 'missing' information but rather may require definition from neighboring processing events. For example, there are known cases where an intronic mutation disrupts the splicing of not only the local intron but also adjacent introns. We present a genome-wide measurement of the order of splicing within human transcripts. The observed order of splicing cannot be explained by a simple kinetic model. Simulations reveal a bias toward a particular, transcript-specific order of intron removal in human genes. We validate an extreme class of intron that can only splice in a multi-intron context. Special categories of splicing such as exon circularization, first and last intron processing, alternative 5 and 3'ss usage and exon skipping are marked by distinct patterns of ordered intron removal. Excessive intronic length and silencer density tend to delay splicing. Shorter introns that contain enhancers splice early.
[Mh] Termos MeSH primário: Genoma Humano
Íntrons
Sítios de Splice de RNA
[Mh] Termos MeSH secundário: Processamento Alternativo
Éxons
Células HEK293
Seres Humanos
Mutação
Poli U/genética
Processamento de RNA
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA Splice Sites); 27416-86-0 (Poly U)
[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:170922
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx661


  2 / 1817 MEDLINE  
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[PMID]:28606943
[Au] Autor:Morita T; Nishino R; Aiba H
[Ad] Endereço:Faculty of Pharmaceutical Sciences, Suzuka University of Medical Sciences, Suzuka, Mie, 513-8670, Japan.
[Ti] Título:Role of the terminator hairpin in the biogenesis of functional Hfq-binding sRNAs.
[So] Source:RNA;23(9):1419-1431, 2017 Sep.
[Is] ISSN:1469-9001
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Rho-independent transcription terminators of the genes encoding bacterial Hfq-binding sRNAs possess a set of seven or more T residues at the 3' end, as noted in previous studies. Here, we have studied the role of the terminator hairpin in the biogenesis of sRNAs focusing on SgrS and RyhB in We constructed variant sRNA genes in which the GC-rich inverted repeat sequences are extended to stabilize the terminator hairpins. We demonstrate that the extension of the hairpin stem leads to generation of heterogeneous transcripts in which the poly(U) tail is shortened. The transcripts with shortened poly(U) tails no longer bind to Hfq and lose the ability to repress the target mRNAs. The shortened transcripts are generated in an in vitro transcription system with purified RNA polymerase, indicating that the generation of shortened transcripts is caused by premature transcription termination. We conclude that the terminator structure of sRNA genes is optimized to generate functional sRNAs. Thus, the Rho-independent terminators of sRNA genes possess two common features: a long T residue stretch that is a prerequisite for generation of functional sRNAs and a moderate strength of hairpin structure that ensures the termination at the seventh or longer position within the consecutive T stretch. The modulation of the termination position at the Rho-independent terminators is critical for biosynthesis of functional sRNAs.
[Mh] Termos MeSH primário: Fator Proteico 1 do Hospedeiro/metabolismo
Sequências Repetidas Invertidas
RNA/genética
RNA/metabolismo
Regiões Terminadoras Genéticas
[Mh] Termos MeSH secundário: Regiões 3' não Traduzidas
Sequência de Bases
Escherichia coli/genética
Escherichia coli/metabolismo
Glucose/metabolismo
Fosfatos/metabolismo
Poli U
Ligação Proteica
RNA/química
Estabilidade de RNA
RNA Bacteriano
RNA Mensageiro/química
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Estresse Fisiológico
Transcrição Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (3' Untranslated Regions); 0 (Host Factor 1 Protein); 0 (Phosphates); 0 (RNA, Bacterial); 0 (RNA, Messenger); 27416-86-0 (Poly U); 63231-63-0 (RNA); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171009
[Lr] Data última revisão:
171009
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170614
[St] Status:MEDLINE
[do] DOI:10.1261/rna.060756.117


  3 / 1817 MEDLINE  
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[PMID]:28546148
[Au] Autor:Zinshteyn B; Rojas-Duran MF; Gilbert WV
[Ad] Endereço:Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
[Ti] Título:Translation initiation factor eIF4G1 preferentially binds yeast transcript leaders containing conserved oligo-uridine motifs.
[So] Source:RNA;23(9):1365-1375, 2017 Sep.
[Is] ISSN:1469-9001
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Translational control of gene expression plays essential roles in cellular stress responses and organismal development by enabling rapid, selective, and localized control of protein production. Translational regulation depends on context-dependent differences in the protein output of mRNAs, but the key mRNA features that distinguish efficiently translated mRNAs are largely unknown. Here, we comprehensively determined the RNA-binding preferences of the eukaryotic initiation factor 4G (eIF4G) to assess whether this core translation initiation factor has intrinsic sequence preferences that may contribute to preferential translation of specific mRNAs. We identified a simple RNA sequence motif-oligo-uridine-that mediates high-affinity binding to eIF4G in vitro. Oligo(U) motifs occur naturally in the transcript leader (TL) of hundreds of yeast genes, and mRNAs with unstructured oligo(U) motifs were enriched in immunoprecipitations against eIF4G. Ribosome profiling following depletion of eIF4G in vivo showed preferentially reduced translation of mRNAs with long TLs, including those that contain oligo(U). Finally, TL oligo(U) elements are enriched in genes with regulatory roles and are conserved between yeast species, consistent with an important cellular function. Taken together, our results demonstrate RNA sequence preferences for a general initiation factor, which cells potentially exploit for translational control of specific mRNAs.
[Mh] Termos MeSH primário: Sítios de Ligação
Fator de Iniciação 4G em Eucariotos/metabolismo
Regulação Fúngica da Expressão Gênica
Motivos de Nucleotídeos
Poli U/metabolismo
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
[Mh] Termos MeSH secundário: Sequência Conservada
Ligação Proteica
Biossíntese de Proteínas
RNA Mensageiro/química
Saccharomyces cerevisiae/genética
Saccharomyces cerevisiae/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Eukaryotic Initiation Factor-4G); 0 (RNA, Messenger); 27416-86-0 (Poly U)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171009
[Lr] Data última revisão:
171009
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170527
[St] Status:MEDLINE
[do] DOI:10.1261/rna.062059.117


  4 / 1817 MEDLINE  
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[PMID]:28104569
[Au] Autor:Zhu Z; Peng M; Zhang J; Tan L
[Ad] Endereço:College of Chemistry, Xiangtan University, Xiangtan 411105, PR China.
[Ti] Título:Interaction of octahedral ruthenium(II) polypyridyl complex [Ru(bpy) (PIP)] with poly(U)·poly(A)*poly(U) triplex: Increasing third-strand stabilization of the triplex without affecting the stability of the duplex.
[So] Source:J Inorg Biochem;169:44-49, 2017 Apr.
[Is] ISSN:1873-3344
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Triple-helical RNA are of interest because of possible biological roles as well as the potential therapeutic uses of these structures, while the stability of triplexes is usually weaker than that of the Watson-Crick base pairing duplex strand due to the electrostatic repulsion between three polyanionic strands. Therefore, how to increase the stability of the specific sequences of triplexes are of importance. In this paper the binding of a Ru(II) complex, [Ru(bpy) (PIP)] (bpy=2.2'-bipyridine, PIP=2-phenyl-1H-imidazo[4,5-f]- [1,10]-phenanthroline), with poly(U)·poly(A)*poly(U) triplex has been investigated by spectrophotometry, spectrofluorometry, viscosimetry and circular dichroism. The results suggest that [Ru(bpy) (PIP)] as a metallointercalator can stabilize poly(U)·poly(A)*poly(U) triplex (where · denotes the Watson-Crick base pairing and * denotes the Hoogsteen base pairing),while it stabilizes third-strand with no obvious effect on the duplex of poly(U)·poly(A), reflecting the binding of this complex with the triplex is favored by the Hoogsteen paired poly(U) third strand to a great extent.
[Mh] Termos MeSH primário: 2,2´-Dipiridil/química
Compostos Organometálicos/química
Poli U/química
RNA/química
Rutênio/química
[Mh] Termos MeSH secundário: Estrutura Molecular
Conformação de Ácido Nucleico
Ligação Proteica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Organometallic Compounds); 27416-86-0 (Poly U); 551W113ZEP (2,2'-Dipyridyl); 63231-63-0 (RNA); 7UI0TKC3U5 (Ruthenium)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170519
[Lr] Data última revisão:
170519
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170121
[St] Status:MEDLINE


  5 / 1817 MEDLINE  
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[PMID]:28052319
[Au] Autor:Castro-Marrero J; Sáez-Francàs N; Santillo D; Alegre J
[Ad] Endereço:CFS/ME Unit, Vall d'Hebron University Hospital, Collserola Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain.
[Ti] Título:Treatment and management of chronic fatigue syndrome/myalgic encephalomyelitis: all roads lead to Rome.
[So] Source:Br J Pharmacol;174(5):345-369, 2017 Mar.
[Is] ISSN:1476-5381
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:This review explores the current evidence on benefits and harms of therapeutic interventions in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and makes recommendations. CFS/ME is a complex, multi-system, chronic medical condition whose pathophysiology remains unknown. No established diagnostic tests exist nor are any FDA-approved drugs available for treatment. Because of the range of symptoms of CFS/ME, treatment approaches vary widely. Studies undertaken have heterogeneous designs and are limited by sample size, length of follow-up, applicability and methodological quality. The use of rintatolimod and rituximab as well as counselling, behavioural and rehabilitation therapy programs may be of benefit for CFS/ME, but the evidence of their effectiveness is still limited. Similarly, adaptive pacing appears to offer some benefits, but the results are debatable: so is the use of nutritional supplements, which may be of value to CFS/ME patients with biochemically proven deficiencies. To summarize, the recommended treatment strategies should include proper administration of nutritional supplements in CFS/ME patients with demonstrated deficiencies and personalized pacing programs to relieve symptoms and improve performance of daily activities, but a larger randomized controlled trial (RCT) evaluation is required to confirm these preliminary observations. At present, no firm conclusions can be drawn because the few RCTs undertaken to date have been small-scale, with a high risk of bias, and have used different case definitions. Further, RCTs are now urgently needed with rigorous experimental designs and appropriate data analysis, focusing particularly on the comparison of outcomes measures according to clinical presentation, patient characteristics, case criteria and degree of disability (i.e. severely ill ME cases or bedridden).
[Mh] Termos MeSH primário: Suplementos Nutricionais
Síndrome de Fadiga Crônica/terapia
Projetos de Pesquisa
[Mh] Termos MeSH secundário: Viés
Síndrome de Fadiga Crônica/fisiopatologia
Seres Humanos
Avaliação de Resultados (Cuidados de Saúde)/métodos
Poli I-C/uso terapêutico
Poli U/uso terapêutico
Ensaios Clínicos Controlados Aleatórios como Assunto
Rituximab/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
27416-86-0 (Poly U); 4F4X42SYQ6 (Rituximab); 94325AJ25N (poly(I).poly(c12,U)); O84C90HH2L (Poly I-C)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170105
[St] Status:MEDLINE
[do] DOI:10.1111/bph.13702


  6 / 1817 MEDLINE  
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[PMID]:28031331
[Au] Autor:Schultz AS; Preussner M; Bunse M; Karni R; Heyd F
[Ad] Endereço:Freie Universität Berlin, Institute of Chemistry and Biochemistry, Berlin, Germany.
[Ti] Título:Activation-Dependent TRAF3 Exon 8 Alternative Splicing Is Controlled by CELF2 and hnRNP C Binding to an Upstream Intronic Element.
[So] Source:Mol Cell Biol;37(7), 2017 Apr 01.
[Is] ISSN:1098-5549
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cell-type-specific and inducible alternative splicing has a fundamental impact on regulating gene expression and cellular function in a variety of settings, including activation and differentiation. We have recently shown that activation-induced skipping of TRAF3 exon 8 activates noncanonical NF-κB signaling upon T cell stimulation, but the regulatory basis for this splicing event remains unknown. Here we identify - and -regulatory elements rendering this splicing switch activation dependent and cell type specific. The -acting element is located 340 to 440 nucleotides upstream of the regulated exon and acts in a distance-dependent manner, since altering the location reduces its activity. A small interfering RNA screen, followed by cross-link immunoprecipitation and mutational analyses, identified CELF2 and hnRNP C as -acting factors that directly bind the regulatory sequence and together mediate increased exon skipping in activated T cells. CELF2 expression levels correlate with TRAF3 exon skipping in several model systems, suggesting that CELF2 is the decisive factor, with hnRNP C being necessary but not sufficient. These data suggest an interplay between CELF2 and hnRNP C as the mechanistic basis for activation-dependent alternative splicing of TRAF3 exon 8 and additional exons and uncover an intronic splicing silencer whose full activity depends on the precise location more than 300 nucleotides upstream of the regulated exon.
[Mh] Termos MeSH primário: Processamento Alternativo/genética
Proteínas CELF/metabolismo
Éxons/genética
Ribonucleoproteínas Nucleares Heterogêneas Grupo C/metabolismo
Íntrons/genética
Ativação Linfocitária/genética
Proteínas do Tecido Nervoso/metabolismo
Fator 3 Associado a Receptor de TNF/genética
[Mh] Termos MeSH secundário: Sítios de Ligação
Células HEK293
Seres Humanos
Poli U/metabolismo
Ligação Proteica/genética
RNA Interferente Pequeno/metabolismo
Elementos Silenciadores Transcricionais/genética
Linfócitos T/imunologia
Fator 3 Associado a Receptor de TNF/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CELF Proteins); 0 (CELF2 protein, human); 0 (Heterogeneous-Nuclear Ribonucleoprotein Group C); 0 (Nerve Tissue Proteins); 0 (RNA, Small Interfering); 0 (TNF Receptor-Associated Factor 3); 27416-86-0 (Poly U)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170917
[Lr] Data última revisão:
170917
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161230
[St] Status:MEDLINE


  7 / 1817 MEDLINE  
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[PMID]:27881476
[Au] Autor:Nowak JS; Hobor F; Downie Ruiz Velasco A; Choudhury NR; Heikel G; Kerr A; Ramos A; Michlewski G
[Ad] Endereço:Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, EH9 3BF, United Kingdom.
[Ti] Título:Lin28a uses distinct mechanisms of binding to RNA and affects miRNA levels positively and negatively.
[So] Source:RNA;23(3):317-332, 2017 Mar.
[Is] ISSN:1469-9001
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Lin28a inhibits the biogenesis of let-7 miRNAs by triggering the polyuridylation and degradation of their precursors by terminal uridylyltransferases TUT4/7 and 3'-5' exoribonuclease Dis3l2, respectively. Previously, we showed that Lin28a also controls the production of neuro-specific miRNA-9 via a polyuridylation-independent mechanism. Here we reveal that the sequences and structural characteristics of pre-let-7 and pre-miRNA-9 are eliciting two distinct modes of binding to Lin28a. We present evidence that Dis3l2 controls miRNA-9 production. Finally, we show that the constitutive expression of untagged Lin28a during neuronal differentiation in vitro positively and negatively affects numerous other miRNAs. Our findings shed light on the role of Lin28a in differentiating cells and on the ways in which one RNA-binding protein can perform multiple roles in the regulation of RNA processing.
[Mh] Termos MeSH primário: Exorribonucleases/genética
MicroRNAs/genética
Neurônios/metabolismo
Precursores de RNA/genética
Proteínas de Ligação a RNA/genética
[Mh] Termos MeSH secundário: Animais
Pareamento de Bases
Sequência de Bases
Diferenciação Celular/efeitos dos fármacos
Linhagem Celular Tumoral
Proteínas de Ligação a DNA/genética
Proteínas de Ligação a DNA/metabolismo
Exorribonucleases/metabolismo
Regulação da Expressão Gênica
Proteínas de Fluorescência Verde/genética
Proteínas de Fluorescência Verde/metabolismo
Células HeLa
Seres Humanos
Camundongos
MicroRNAs/metabolismo
Neurônios/citologia
Neurônios/efeitos dos fármacos
Conformação de Ácido Nucleico
Células-Tronco Pluripotentes/citologia
Células-Tronco Pluripotentes/efeitos dos fármacos
Células-Tronco Pluripotentes/metabolismo
Poli U/metabolismo
Ligação Proteica
Clivagem do RNA
RNA Nucleotidiltransferases/genética
RNA Nucleotidiltransferases/metabolismo
Precursores de RNA/metabolismo
Proteínas de Ligação a RNA/metabolismo
Proteínas Recombinantes de Fusão/genética
Proteínas Recombinantes de Fusão/metabolismo
Tretinoína/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA-Binding Proteins); 0 (LIN28B protein, human); 0 (MIRN92 microRNA, human); 0 (MicroRNAs); 0 (RNA Precursors); 0 (RNA-Binding Proteins); 0 (Recombinant Fusion Proteins); 0 (ZCCHC11 protein, human); 0 (mirnlet7 microRNA, human); 147336-22-9 (Green Fluorescent Proteins); 27416-86-0 (Poly U); 5688UTC01R (Tretinoin); EC 2.7.7.- (RNA Nucleotidyltransferases); EC 2.7.7.- (Zcchc6 protein, human); EC 3.1.- (DIS3L2 protein, human); EC 3.1.- (Exoribonucleases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161125
[St] Status:MEDLINE
[do] DOI:10.1261/rna.059196.116


  8 / 1817 MEDLINE  
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[PMID]:27865825
[Au] Autor:Baranovskaya MD; Ugarov VI; Chetverina HV; Chetverin AB
[Ad] Endereço:Institute of Protein Research of the Russian Academy of Sciences, 142290 Pushchino, Moscow Region, Russia.
[Ti] Título:Removal of protein S1 from Escherichia coli ribosomes without the use of affinity chromatography.
[So] Source:Anal Biochem;517:53-55, 2017 Jan 15.
[Is] ISSN:1096-0309
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The paper reports an inexpensive and efficient procedure for the removal of protein S1 from E. coli ribosomes. It comprises incubation of ribosomes in a pyrimidine polyribonucleotide solution followed by centrifugation of the sample through a sucrose cushion. To avoid co-sedimentation of the S1-bound polypyrimidine with the ribosomes, its length should not exceed several hundred nucleotides. Unlike popular affinity chromatography through a poly(U) Sepharose or poly(U) cellulose column, the method tolerates limited polyribonucleotide degradation by eventual traces of ribonucleases, and can readily be incorporated into standard protocols for the isolation of ribosomes by centrifugation.
[Mh] Termos MeSH primário: Proteínas de Escherichia coli/isolamento & purificação
Escherichia coli/química
Proteínas Ribossômicas/isolamento & purificação
Ribossomos/química
[Mh] Termos MeSH secundário: Centrifugação com Gradiente de Concentração/métodos
Cromatografia de Afinidade
Poli U/química
Sacarose/análogos & derivados
Sacarose/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Escherichia coli Proteins); 0 (Ribosomal Proteins); 0 (Sucrocide); 0 (ribosomal protein S1, E coli); 27416-86-0 (Poly U); 57-50-1 (Sucrose)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170508
[Lr] Data última revisão:
170508
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161121
[St] Status:MEDLINE


  9 / 1817 MEDLINE  
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[PMID]:27287059
[Au] Autor:Li J; Sun Y; Zhu Z; Zhao H; Tan L
[Ad] Endereço:College of Chemistry, Xiangtan University, Xiangtan 411105, PR China.
[Ti] Título:Binding properties of ruthenium(II) complexes [Ru(bpy)2(ppn)](2+) and [Ru(phen)2(ppn)](2+) with triplex RNA: As molecular "light switches" and stabilizers for poly(U)·poly(A)*poly(U) triplex.
[So] Source:J Inorg Biochem;161:128-33, 2016 Aug.
[Is] ISSN:1873-3344
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Stable RNA triplexes play key roles in many biological processes, while triplexes are thermodynamically less stable than the corresponding duplexes due to the Hoogsteen base pairing. To understand the factors affecting the stabilization of RNA triplexes by octahedral ruthenium(II) complexes, the binding of [Ru(bpy)2(ppn)](2+) (1, bpy=2,2'-bipyridine, ppn=2,4-diaminopyrimido[5,6-b]dipyrido[2,3-f:2',3'-h]quinoxaline) and [Ru(phen)2(ppn)](2+) (2, phen=1,10-phenanthroline) to poly(U)·poly(A)*poly(U) (· denotes the Watson-Crick base pairing and * denotes the Hoogsteen base pairing) has been investigated. The main results obtained here suggest that complexes 1 and 2 can serve as molecular "light switches" and stabilizers for poly(U)·poly(A)*poly(U), while the effectiveness of complex 2 are more marked, suggesting that the hydrophobicity of ancillary ligands has a significant effect on the two Ru(II) complexes binding to poly(U)·poly(A)*poly(U). This study further advances our knowledge on the binding of RNA triplexes with metal complexes, particularly with octahedral ruthenium polypyridyl complexes.
[Mh] Termos MeSH primário: Poli A/química
Poli U/química
Estabilidade de RNA
RNA/química
Rutênio/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
24937-83-5 (Poly A); 27416-86-0 (Poly U); 63231-63-0 (RNA); 7UI0TKC3U5 (Ruthenium)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170904
[Lr] Data última revisão:
170904
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160612
[St] Status:MEDLINE


  10 / 1817 MEDLINE  
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[PMID]:27045557
[Au] Autor:Mitchell WM
[Ad] Endereço:a Department of Pathology, Microbiology & Immunology , Vanderbilt University , Nashville , USA.
[Ti] Título:Efficacy of rintatolimod in the treatment of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME).
[So] Source:Expert Rev Clin Pharmacol;9(6):755-70, 2016 Jun.
[Is] ISSN:1751-2441
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Chronic fatigue syndrome/ Myalgic encephalomyelitis (CFS/ME) is a poorly understood seriously debilitating disorder in which disabling fatigue is an universal symptom in combination with a variety of variable symptoms. The only drug in advanced clinical development is rintatolimod, a mismatched double stranded polymer of RNA (dsRNA). Rintatolimod is a restricted Toll-Like Receptor 3 (TLR3) agonist lacking activation of other primary cellular inducers of innate immunity (e.g.- cytosolic helicases). Rintatolimod also activates interferon induced proteins that require dsRNA for activity (e.g.- 2'-5' adenylate synthetase, protein kinase R). Rintatolimod has achieved statistically significant improvements in primary endpoints in Phase II and Phase III double-blind, randomized, placebo-controlled clinical trials with a generally well tolerated safety profile and supported by open-label trials in the United States and Europe. The chemistry, mechanism of action, clinical trial data, and current regulatory status of rintatolimod for CFS/ME including current evidence for etiology of the syndrome are reviewed.
[Mh] Termos MeSH primário: Síndrome de Fadiga Crônica/tratamento farmacológico
Poli I-C/uso terapêutico
Poli U/uso terapêutico
Receptor 3 Toll-Like/agonistas
[Mh] Termos MeSH secundário: Animais
Síndrome de Fadiga Crônica/fisiopatologia
Seres Humanos
Imunidade Inata/imunologia
Poli I-C/efeitos adversos
Poli I-C/farmacologia
Poli U/efeitos adversos
Poli U/farmacologia
RNA de Cadeia Dupla/metabolismo
Ensaios Clínicos Controlados Aleatórios como Assunto
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (RNA, Double-Stranded); 0 (Toll-Like Receptor 3); 27416-86-0 (Poly U); 94325AJ25N (poly(I).poly(c12,U)); O84C90HH2L (Poly I-C)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160406
[St] Status:MEDLINE
[do] DOI:10.1586/17512433.2016.1172960



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