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Pesquisa : D12.776.157.725.750 [Categoria DeCS]
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  1 / 417 MEDLINE  
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[PMID]:28934473
[Au] Autor:Yeh CS; Chang SL; Chen JH; Wang HK; Chou YC; Wang CH; Huang SH; Larson A; Pleiss JA; Chang WH; Chang TH
[Ad] Endereço:Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.
[Ti] Título:The conserved AU dinucleotide at the 5' end of nascent U1 snRNA is optimized for the interaction with nuclear cap-binding-complex.
[So] Source:Nucleic Acids Res;45(16):9679-9693, 2017 Sep 19.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Splicing is initiated by a productive interaction between the pre-mRNA and the U1 snRNP, in which a short RNA duplex is established between the 5' splice site of a pre-mRNA and the 5' end of the U1 snRNA. A long-standing puzzle has been why the AU dincucleotide at the 5'-end of the U1 snRNA is highly conserved, despite the absence of an apparent role in the formation of the duplex. To explore this conundrum, we varied this AU dinucleotide into all possible permutations and analyzed the resulting molecular consequences. This led to the unexpected findings that the AU dinucleotide dictates the optimal binding of cap-binding complex (CBC) to the 5' end of the nascent U1 snRNA, which ultimately influences the utilization of U1 snRNP in splicing. Our data also provide a structural interpretation as to why the AU dinucleotide is conserved during evolution.
[Mh] Termos MeSH primário: Proteínas de Ligação ao Cap de RNA/metabolismo
RNA Nuclear Pequeno/química
RNA Nuclear Pequeno/metabolismo
[Mh] Termos MeSH secundário: Pareamento de Bases
Simulação de Acoplamento Molecular
Complexo Proteico Nuclear de Ligação ao Cap/genética
Complexo Proteico Nuclear de Ligação ao Cap/metabolismo
Proteínas de Ligação ao Cap de RNA/genética
Precursores de RNA/metabolismo
Processamento de RNA
RNA Nuclear Pequeno/genética
Ribonucleoproteína Nuclear Pequena U1/genética
Ribonucleoproteína Nuclear Pequena U1/metabolismo
Proteínas de Saccharomyces cerevisiae/genética
Proteínas de Saccharomyces cerevisiae/metabolismo
Leveduras/genética
Leveduras/crescimento & desenvolvimento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CBC2 protein, S cerevisiae); 0 (Nuclear Cap-Binding Protein Complex); 0 (RNA Cap-Binding Proteins); 0 (RNA Precursors); 0 (RNA, Small Nuclear); 0 (Ribonucleoprotein, U1 Small Nuclear); 0 (Saccharomyces cerevisiae Proteins); 0 (U1 small nuclear RNA)
[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/gkx608


  2 / 417 MEDLINE  
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[PMID]:28698298
[Au] Autor:Peter D; Weber R; Sandmeir F; Wohlbold L; Helms S; Bawankar P; Valkov E; Igreja C; Izaurralde E
[Ad] Endereço:Department of Biochemistry, Max Planck Institute for Developmental Biology, 72076 Tübingen, Germany.
[Ti] Título:GIGYF1/2 proteins use auxiliary sequences to selectively bind to 4EHP and repress target mRNA expression.
[So] Source:Genes Dev;31(11):1147-1161, 2017 Jun 01.
[Is] ISSN:1549-5477
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The eIF4E homologous protein (4EHP) is thought to repress translation by competing with eIF4E for binding to the 5' cap structure of specific mRNAs to which it is recruited through interactions with various proteins, including the GRB10-interacting GYF (glycine-tyrosine-phenylalanine domain) proteins 1 and 2 (GIGYF1/2). Despite its similarity to eIF4E, 4EHP does not interact with eIF4G and therefore fails to initiate translation. In contrast to eIF4G, GIGYF1/2 bind selectively to 4EHP but not eIF4E. Here, we present crystal structures of the 4EHP-binding regions of GIGYF1 and GIGYF2 in complex with 4EHP, which reveal the molecular basis for the selectivity of the GIGYF1/2 proteins for 4EHP. Complementation assays in a GIGYF1/2-null cell line using structure-based mutants indicate that 4EHP requires interactions with GIGYF1/2 to down-regulate target mRNA expression. Our studies provide structural insights into the assembly of 4EHP-GIGYF1/2 repressor complexes and reveal that rather than merely facilitating 4EHP recruitment to transcripts, GIGYF1/2 proteins are required for repressive activity.
[Mh] Termos MeSH primário: Proteínas de Transporte/química
Proteínas de Transporte/metabolismo
Regulação da Expressão Gênica/genética
Proteínas de Ligação ao Cap de RNA/metabolismo
RNA Mensageiro/genética
[Mh] Termos MeSH secundário: Proteínas de Transporte/genética
Linhagem Celular
Cristalização
Células HEK293
Seres Humanos
Modelos Moleculares
Mutação
Ligação Proteica/genética
Estabilidade Proteica
Estrutura Quaternária de Proteína
Proteínas de Ligação ao Cap de RNA/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Carrier Proteins); 0 (EIF4E2 protein, human); 0 (GIGYF1 protein, human); 0 (GIGYF2 protein, human); 0 (RNA Cap-Binding Proteins); 0 (RNA, Messenger)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171025
[Lr] Data última revisão:
171025
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170713
[St] Status:MEDLINE
[do] DOI:10.1101/gad.299420.117


  3 / 417 MEDLINE  
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[PMID]:28031482
[Au] Autor:Wang CY; Wang YT; Hsiao WY; Wang SW
[Ad] Endereço:Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli County 350, Taiwan, Republic of China.
[Ti] Título:Involvement of fission yeast Pdc2 in RNA degradation and P-body function.
[So] Source:RNA;23(4):493-503, 2017 Apr.
[Is] ISSN:1469-9001
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In this study we identified Pdc2, the fission yeast ortholog of human Pat1b protein, which forms a complex with Lsm1-7 and plays a role in coupling deadenylation and decapping. The involvement of Pdc2 in RNA degradation and P-body function was also determined. We found that Pdc2 interacts with Dcp2 and is required for decapping in vivo. Although not absolutely essential for P-body assembly, overexpression of Pdc2 enhanced P-body formation even in the absence of Pdc1, the fission yeast functional homolog of human Edc4 protein, indicating that Pdc2 also plays a role in P-body formation. Intriguingly, in the absence of Pdc2, Lsm1 was found to accumulate in the nucleus, suggesting that Pdc2 shuttling between nucleus and cytoplasm plays a role in decreasing the nuclear concentration of Lsm1 to increase Lsm1 in the cytoplasm. Furthermore, unlike other components of P-bodies, the deadenylase Ccr4 did not accumulate in P-bodies in cells growing under favorable conditions and was only recruited to P-bodies after deprivation of glucose in a Pdc2-Lsm1-dependent manner, indicating a function of Pdc2 in cellular response to environmental stress. In supporting this idea, mutants are defective in recovery from glucose starvation with a much longer time to re-enter the cell cycle. In keeping with the notion that Pat1 is a nucleocytoplasmic protein, functioning also in the nucleus, we found that Pdc2 physically and genetically interacts with the nuclear 5'-3' exonuclease Dhp1. A function of Pdc2-Lsm1, in concert with Dhp1, regulating RNA by promoting its decapping/destruction in the nucleus was suggested.
[Mh] Termos MeSH primário: Exorribonucleases/genética
Regulação Fúngica da Expressão Gênica
Piruvato Descarboxilase/genética
Estabilidade de RNA
RNA Fúngico/genética
Proteínas de Schizosaccharomyces pombe/genética
Schizosaccharomyces/genética
Fatores de Transcrição/genética
[Mh] Termos MeSH secundário: Transporte Ativo do Núcleo Celular
Sequência de Bases
Ciclo Celular/genética
Núcleo Celular/genética
Núcleo Celular/metabolismo
Citoplasma/genética
Citoplasma/metabolismo
Proteínas de Ligação a DNA/genética
Proteínas de Ligação a DNA/metabolismo
Exorribonucleases/metabolismo
Proteínas Fúngicas/genética
Proteínas Fúngicas/metabolismo
Glucose/deficiência
Glucose/farmacologia
Seres Humanos
Proteínas Serina-Treonina Quinases/genética
Proteínas Serina-Treonina Quinases/metabolismo
Piruvato Descarboxilase/metabolismo
Proteínas de Ligação ao Cap de RNA/genética
Proteínas de Ligação ao Cap de RNA/metabolismo
RNA Fúngico/metabolismo
Proteínas de Ligação a RNA/genética
Proteínas de Ligação a RNA/metabolismo
Schizosaccharomyces/efeitos dos fármacos
Schizosaccharomyces/metabolismo
Proteínas de Schizosaccharomyces pombe/metabolismo
Fatores de Transcrição/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ccr4 protein, S pombe); 0 (DNA-Binding Proteins); 0 (Dcp2 protein, S pombe); 0 (Fungal Proteins); 0 (PATL1 protein, human); 0 (RNA Cap-Binding Proteins); 0 (RNA, Fungal); 0 (RNA-Binding Proteins); 0 (Schizosaccharomyces pombe Proteins); 0 (Transcription Factors); EC 2.7.1.- (ran1 protein, S pombe); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); EC 3.1.- (Exoribonucleases); EC 3.1.- (dhp1protein, S pombe); EC 4.1.1.1 (Pyruvate Decarboxylase); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161230
[St] Status:MEDLINE
[do] DOI:10.1261/rna.059766.116


  4 / 417 MEDLINE  
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[PMID]:27911187
[Au] Autor:Bukhari SI; Vasudevan S
[Ad] Endereço:a Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School , Boston , MA , USA.
[Ti] Título:FXR1a-associated microRNP: A driver of specialized non-canonical translation in quiescent conditions.
[So] Source:RNA Biol;14(2):137-145, 2017 Feb.
[Is] ISSN:1555-8584
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Eukaryotic protein synthesis is a multifaceted process that requires coordination of a set of translation factors in a particular cellular state. During normal growth and proliferation, cells generally make their proteome via conventional translation that utilizes canonical translation factors. When faced with environmental stress such as growth factor deprivation, or in response to biological cues such as developmental signals, cells can reduce canonical translation. In this situation, cells adapt alternative modes of translation to make specific proteins necessary for required biological functions under these distinct conditions. To date, a number of alternative translation mechanisms have been reported, which include non-canonical, cap dependent translation and cap independent translation such as IRES mediated translation. Here, we discuss one of the alternative modes of translation mediated by a specialized microRNA complex, FXR1a-microRNP that promotes non-canonical, cap dependent translation in quiescent conditions, where canonical translation is reduced due to low mTOR activity.
[Mh] Termos MeSH primário: Proteínas Argonauta/metabolismo
Proteína do X Frágil de Retardo Mental/metabolismo
MicroRNAs/genética
MicroRNAs/metabolismo
[Mh] Termos MeSH secundário: Animais
Fator de Iniciação 4G em Eucariotos/metabolismo
Exorribonucleases/metabolismo
Regulação da Expressão Gênica
Seres Humanos
Poli A/genética
Ligação Proteica
Biossíntese de Proteínas
Proteínas de Ligação ao Cap de RNA/metabolismo
Capuzes de RNA/metabolismo
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Serina-Treonina Quinases TOR/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Argonaute Proteins); 0 (Eukaryotic Initiation Factor-4G); 0 (MicroRNAs); 0 (RNA Cap-Binding Proteins); 0 (RNA Caps); 0 (RNA, Messenger); 139135-51-6 (Fragile X Mental Retardation Protein); 24937-83-5 (Poly A); EC 2.7.1.1 (TOR Serine-Threonine Kinases); EC 3.1.- (Exoribonucleases); EC 3.1.13.4 (poly(A)-specific ribonuclease)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161203
[St] Status:MEDLINE
[do] DOI:10.1080/15476286.2016.1265197


  5 / 417 MEDLINE  
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[PMID]:28060265
[Au] Autor:Timpano S; Melanson G; Evagelou SL; Guild BD; Specker EJ; Uniacke J
[Ad] Endereço:Department of Molecular and Cellular Biology, University of Guelph.
[Ti] Título:Analysis of Cap-binding Proteins in Human Cells Exposed to Physiological Oxygen Conditions.
[So] Source:J Vis Exp;(118), 2016 Dec 28.
[Is] ISSN:1940-087X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Translational control is a focal point of gene regulation, especially during periods of cellular stress. Cap-dependent translation via the eIF4F complex is by far the most common pathway to initiate protein synthesis in eukaryotic cells, but stress-specific variations of this complex are now emerging. Purifying cap-binding proteins with an affinity resin composed of Agarose-linked m GTP (a 5' mRNA cap analog) is a useful tool to identify factors involved in the regulation of translation initiation. Hypoxia (low oxygen) is a cellular stress encountered during fetal development and tumor progression, and is highly dependent on translation regulation. Furthermore, it was recently reported that human adult organs have a lower oxygen content (physioxia 1-9% oxygen) that is closer to hypoxia than the ambient air where cells are routinely cultured. With the ongoing characterization of a hypoxic eIF4F complex (eIF4F ), there is increasing interest in understanding oxygen-dependent translation initiation through the 5' mRNA cap. We have recently developed a human cell culture method to analyze cap-binding proteins that are regulated by oxygen availability. This protocol emphasizes that cell culture and lysis be performed in a hypoxia workstation to eliminate exposure to oxygen. Cells must be incubated for at least 24 hr for the liquid media to equilibrate with the atmosphere within the workstation. To avoid this limitation, pre-conditioned media (de-oxygenated) can be added to cells if shorter time points are required. Certain cap-binding proteins require interactions with a second base or can hydrolyze the m GTP, therefore some cap interactors may be missed in the purification process. Agarose-linked to enzymatically resistant cap analogs may be substituted in this protocol. This method allows the user to identify novel oxygen-regulated translation factors involved in cap-dependent translation.
[Mh] Termos MeSH primário: Técnicas de Cultura de Células
Oxigênio/fisiologia
Proteínas de Ligação ao Cap de RNA/metabolismo
[Mh] Termos MeSH secundário: Meios de Cultura/química
Fator de Iniciação 4F em Eucariotos/metabolismo
Seres Humanos
Biossíntese de Proteínas
Capuzes de RNA
[Pt] Tipo de publicação:JOURNAL ARTICLE; VIDEO-AUDIO MEDIA
[Nm] Nome de substância:
0 (Culture Media); 0 (Eukaryotic Initiation Factor-4F); 0 (RNA Cap-Binding Proteins); 0 (RNA Caps); S88TT14065 (Oxygen)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170814
[Lr] Data última revisão:
170814
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170107
[St] Status:MEDLINE
[do] DOI:10.3791/55112


  6 / 417 MEDLINE  
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[PMID]:27578149
[Au] Autor:Frydryskova K; Masek T; Borcin K; Mrvova S; Venturi V; Pospisek M
[Ad] Endereço:Laboratory of RNA Biochemistry, Department of Genetics and Microbiology, Faculty of Science, Charles University in Prague, Vinicná 5, 128 00, Prague 2, Czech Republic.
[Ti] Título:Distinct recruitment of human eIF4E isoforms to processing bodies and stress granules.
[So] Source:BMC Mol Biol;17(1):21, 2016 Aug 30.
[Is] ISSN:1471-2199
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Eukaryotic translation initiation factor 4E (eIF4E) plays a pivotal role in the control of cap-dependent translation initiation, modulates the fate of specific mRNAs, occurs in processing bodies (PBs) and is required for formation of stress granules (SGs). In this study, we focused on the subcellular localization of a representative compendium of eIF4E protein isoforms, particularly on the less studied members of the human eIF4E protein family, eIF4E2 and eIF4E3. RESULTS: We showed that unlike eIF4E1, its less studied isoform eIF4E3_A, encoded by human chromosome 3, localized to stress granules but not PBs upon both heat shock and arsenite stress. Furthermore, we found that eIF4E3_A interacts with human translation initiation factors eIF4G1, eIF4G3 and PABP1 in vivo and sediments into the same fractions as canonical eIF4E1 during polysome analysis in sucrose gradients. Contrary to this finding, the truncated human eIF4E3 isoform, eIF4E3_B, showed no localization to SGs and no binding to eIF4G. We also highlighted that eIF4E2 may exhibit distinct functions under different stresses as it readily localizes to P-bodies during arsenite and heat stresses, whereas it is redirected to stress granules only upon heat shock. We extended our study to a number of protein variants, arising from alternative mRNA splicing, of each of the three eIF4E isoforms. Our results surprisingly uncovered differences in the ability of eIF4E1_1 and eIF4E1_3 to form stress granules in response to cellular stresses. CONCLUSION: Our comparison of all three human eIF4E isoforms and their protein variants enriches the intriguing spectrum of roles attributed to the eukaryotic initiation translation factors of the 4E family, which exhibit a distinctive localization within different RNA granules under different stresses. The localization of eIF4E3_A to stress granules, but not to processing bodies, along with its binding to eIF4G and PABP1 suggests a role of human eIF4E3_A in translation initiation rather than its involvement in a translational repression and mRNA decay and turnover. The localization of eIF4E2 to stress granules under heat shock but not arsenite stress indicates its distinct function in cellular response to these stresses and points to the variable protein content of SGs as a consequence of different stress insults.
[Mh] Termos MeSH primário: Fator de Iniciação 4E em Eucariotos/metabolismo
Resposta ao Choque Térmico
Estresse Oxidativo
Proteínas de Ligação ao Cap de RNA/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Linhagem Celular
Clonagem Molecular
Citosol/metabolismo
Fator de Iniciação 4E em Eucariotos/análise
Fator de Iniciação 4E em Eucariotos/genética
Células HEK293
Seres Humanos
Proteína I de Ligação a Poli(A)/análise
Proteína I de Ligação a Poli(A)/metabolismo
Proteínas de Ligação ao Cap de RNA/análise
Proteínas de Ligação ao Cap de RNA/genética
RNA Mensageiro/genética
Alinhamento de Sequência
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (EIF4E2 protein, human); 0 (Eukaryotic Initiation Factor-4E); 0 (Poly(A)-Binding Protein I); 0 (RNA Cap-Binding Proteins); 0 (RNA, Messenger); 0 (eIF4E3 protein, human)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170913
[Lr] Data última revisão:
170913
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160901
[St] Status:MEDLINE
[do] DOI:10.1186/s12867-016-0072-x


  7 / 417 MEDLINE  
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[PMID]:27514009
[Au] Autor:Vizzini A; Bonura A; Longo V; Sanfratello MA; Parrinello D; Cammarata M; Colombo P
[Ad] Endereço:Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Via Archirafi 18, Palermo, Italy.
[Ti] Título:LPS injection reprograms the expression and the 3' UTR of a CAP gene by alternative polyadenylation and the formation of a GAIT element in Ciona intestinalis.
[So] Source:Mol Immunol;77:174-83, 2016 Sep.
[Is] ISSN:1872-9142
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The diversification of cellular functions is one of the major characteristics of multicellular organisms which allow cells to modulate their gene expression, leading to the formation of transcripts and proteins with different functions and concentrations in response to different stimuli. CAP genes represent a widespread family of proteins belonging to the cysteine-rich secretory protein, antigen 5 and pathogenesis-related 1 superfamily which, it has been proposed, play key roles in the infection process and the modulation of immune responses in host animals. The ascidian Ciona intestinalis represents a group of proto-chordates with an exclusively innate immune system that has been widely studied in the field of comparative and developmental immunology. Using this biological system, we describe the identification of a novel APA mechanism by which an intronic polyadenylation signal is activated by LPS injection, leading to the formation of a shorter CAP mRNA capable of expressing the first CAP exon plus 19 amino acid residues whose sequence is contained within the first intron of the annotated gene. Furthermore, such an APA event causes the expression of a translational controlling cis-acting GAIT element which is not present in the previously isolated CAP isoform and identified in the 3'-UTR of other immune-related genes, suggesting an intriguing scenario in which both transcriptional and post-transcriptional control mechanisms are involved in the activation of the CAP gene during inflammatory response in C. intestinalis.
[Mh] Termos MeSH primário: Ciona intestinalis/genética
Ciona intestinalis/imunologia
Regulação da Expressão Gênica/genética
Proteínas de Ligação ao Cap de RNA/genética
Elementos Reguladores de Transcrição/genética
[Mh] Termos MeSH secundário: Regiões 3' não Traduzidas/genética
Regiões 3' não Traduzidas/imunologia
Sequência de Aminoácidos
Animais
Sequência de Bases
Perfilação da Expressão Gênica
Regulação da Expressão Gênica/imunologia
Hibridização In Situ
Lipopolissacarídeos/imunologia
Poliadenilação
Reação em Cadeia da Polimerase
Elementos Reguladores de Transcrição/imunologia
Alinhamento de Sequência
Transcriptoma
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (3' Untranslated Regions); 0 (Lipopolysaccharides); 0 (RNA Cap-Binding Proteins)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170821
[Lr] Data última revisão:
170821
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160812
[St] Status:MEDLINE


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[PMID]:27494431
[Au] Autor:Hett EC; Kyne RE; Gopalsamy A; Tones MA; Xu H; Thio GL; Nolan E; Jones LH
[Ad] Endereço:Medicine Design, Pfizer , 610 Main Street, Cambridge, Massachusetts 02139, United States.
[Ti] Título:Selectivity Determination of a Small Molecule Chemical Probe Using Protein Microarray and Affinity Capture Techniques.
[So] Source:ACS Comb Sci;18(10):611-615, 2016 Oct 10.
[Is] ISSN:2156-8944
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Small molecule selectivity is an essential component of candidate drug selection and target validation. New technologies are required to better understand off-target effects, with particular emphasis needed on broad protein profiling. Here, we describe the use of a tritiated chemical probe and a 9000 human protein microarray to discern the binding selectivity of an inhibitor of the mRNA decapping scavenger enzyme DcpS. An immobilized m GTP resin was also used to assess the selectivity of a DcpS inhibitor against mRNA cap-associated proteins in whole cell extracts. These studies confirm the exquisite selectivity of diaminoquinazoline DcpS inhibitors, and highlight the utility of relatively simple protein microarray and affinity enrichment technologies in drug discovery and chemical biology.
[Mh] Termos MeSH primário: Endorribonucleases/análise
Sondas Moleculares/química
Quinazolinas/química
Proteínas de Ligação ao Cap de RNA/análise
[Mh] Termos MeSH secundário: Catálise
Células Cultivadas
Endorribonucleases/antagonistas & inibidores
Endorribonucleases/genética
Seres Humanos
Leucócitos Mononucleares/química
Análise Serial de Proteínas
RNA Mensageiro/genética
Proteína 2 de Sobrevivência do Neurônio Motor/análise
Trítio
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Molecular Probes); 0 (PF-06652474); 0 (Quinazolines); 0 (RNA Cap-Binding Proteins); 0 (RNA, Messenger); 0 (SMN2 protein, human); 0 (Survival of Motor Neuron 2 Protein); 10028-17-8 (Tritium); EC 3.1.- (Endoribonucleases); EC 3.1.27.- (DcpS protein, human)
[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:160806
[St] Status:MEDLINE


  9 / 417 MEDLINE  
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[PMID]:27434131
[Au] Autor:Chowdhury A; Kalurupalle S; Tharun S
[Ad] Endereço:Department of Biochemistry, Uniformed Services University of the Health Sciences (USUHS), 4301, Jones Bridge Road, Bethesda, MD, 20814-4799, United States of America.
[Ti] Título:Mutagenic Analysis of the C-Terminal Extension of Lsm1.
[So] Source:PLoS One;11(7):e0158876, 2016.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The Sm-like proteins (also known as Lsm proteins) are ubiquitous in nature and exist as hexa or heptameric RNA binding complexes. They are characterized by the presence of the Sm-domain. The Lsm1 through Lsm7 proteins are highly conserved in eukaryotes and they form a hetero-octameric complex together with the protein Pat1. The Lsm1-7-Pat1 complex plays a key role in mRNA decapping and 3'-end protection and therefore is required for normal mRNA decay rates in vivo. Lsm1 is a key subunit that is critical for the unique RNA binding properties of this complex. We showed earlier that unlike most Sm-like proteins, Lsm1 uniquely requires both its Sm domain and its C-terminal extension to contribute to the function of the Lsm1-7-Pat1 complex and that the C-terminal segment can associate with the rest of the complex and support the function even in trans. The studies presented here identify a set of residues at the very C-terminal end of Lsm1 to be functionally important and suggest that these residues support the function of the Lsm1-7-Pat1 complex by facilitating RNA binding either directly or indirectly.
[Mh] Termos MeSH primário: Mutagênese/genética
Proteínas de Ligação ao Cap de RNA/química
Proteínas de Ligação a RNA/química
Proteínas de Saccharomyces cerevisiae/química
[Mh] Termos MeSH secundário: Seres Humanos
Conformação Molecular
Complexos Multiproteicos/química
Complexos Multiproteicos/genética
Mutação/genética
Desnaturação de Ácido Nucleico/genética
Ligação Proteica
Proteínas de Ligação ao Cap de RNA/genética
Estabilidade de RNA
Proteínas de Ligação a RNA/genética
Saccharomyces cerevisiae/química
Saccharomyces cerevisiae/genética
Proteínas de Saccharomyces cerevisiae/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (LSM1 protein, S cerevisiae); 0 (Multiprotein Complexes); 0 (PAT1 protein, S cerevisiae); 0 (RNA Cap-Binding Proteins); 0 (RNA-Binding Proteins); 0 (Saccharomyces cerevisiae Proteins)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170726
[Lr] Data última revisão:
170726
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160720
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0158876


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[PMID]:27272726
[Au] Autor:Yuan S; Chu H; Zhang K; Ye J; Singh K; Kao RY; Chow BK; Zhou J; Zheng BJ
[Ad] Endereço:Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
[Ti] Título:A novel small-molecule compound disrupts influenza A virus PB2 cap-binding and inhibits viral replication.
[So] Source:J Antimicrob Chemother;71(9):2489-97, 2016 Sep.
[Is] ISSN:1460-2091
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: The conserved residues 318-483 in the PB2 subunit of influenza A polymerase is an independently folded cap-binding domain (PB2cap) that exhibits a distinct binding mode from other host cap-binding proteins, which suggests that PB2cap might be an ideal drug target. This study aimed to identify a new class of anti-influenza inhibitors that specifically disrupts the interaction between PB2cap and host cap structures. METHODS: An innovative fluorescence polarization assay was established for primary screening, followed by cap-binding inhibitory activity, antiviral efficacy and cytotoxicity evaluations of the selected compounds. The best compound was characterized by multi-cycle virus growth assay, cross-protection test, synergism evaluation, mini-replicon assay, binding affinity analysis, docking simulation and mouse study. RESULTS: Several PB2 cap-binding inhibitors were discovered. The compound 7-(4-hydroxy-2-oxo-2H-chromen-3-yl)-6H,7H,8H-chromeno[3',4':5,6]pyrano[3,2-c]chromene-6,8-dione, designated PB2-39, was identified as a potent inhibitor of replication of multiple subtypes of influenza A virus, including H1N1, H3N2, H5N1, H7N7, H7N9 and H9N2 in vitro and H1N1, H5N1 and H7N9 in vivo. Combinational treatment with the influenza virus release inhibitor zanamivir and PB2-39 exerted a synergistic anti-influenza effect. Mechanistic experiments supported that PB2-39 suppressed viral polymerase activity. Docking and binding affinity analyses demonstrated that PB2-39 interacted with the PB2 cap-binding pocket, suggesting its role as a cap-binding competitor. CONCLUSIONS: Our study provides new insights for the strategic development of novel cap-binding inhibitors of influenza A viruses.
[Mh] Termos MeSH primário: Antivirais/isolamento & purificação
Antivirais/farmacologia
Vírus da Influenza A/efeitos dos fármacos
Vírus da Influenza A/fisiologia
Proteínas de Ligação ao Cap de RNA/antagonistas & inibidores
Proteínas Virais/antagonistas & inibidores
Replicação Viral/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Antivirais/toxicidade
Linhagem Celular
Sobrevivência Celular/efeitos dos fármacos
Modelos Animais de Doenças
Sinergismo Farmacológico
Feminino
Polarização de Fluorescência
Seres Humanos
Camundongos Endogâmicos BALB C
Infecções por Orthomyxoviridae/tratamento farmacológico
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (PB2 protein, influenza virus); 0 (RNA Cap-Binding Proteins); 0 (Viral Proteins)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170815
[Lr] Data última revisão:
170815
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160609
[St] Status:MEDLINE
[do] DOI:10.1093/jac/dkw194



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