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Pesquisa : D08.811.913.696.445.735.720.500 [Categoria DeCS]
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[PMID]:28918745
[Au] Autor:Sogorin EA; Selikhanov GK; Agalarov SC
[Ad] Endereço:Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region, 142290, Russia. sultan@vega.protres.ru.
[Ti] Título:Coupling of Translation Initiation and Termination Does Not Depend on the Mode of Initiation.
[So] Source:Biochemistry (Mosc);82(7):816-820, 2017 Jul.
[Is] ISSN:1608-3040
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Recently we described a novel phenomenon observed during eukaryotic translation in a cell-free system: the coupling of initiation and termination on different mRNA molecules. Here we show that the phenomenon does not depend on a special mode of initiation. The mRNAs with certain leader sequences known to require different determinants for successful initiation were examined. Even in a case of using the intergenic internal ribosome entry site (IRES) of cricket paralysis virus RNA as the leader sequence, while no initiation factors are required, the effect of coupling is well expressed, including trials in the presence of hippuristanol as an inhibitor of eIF4A. Thus, the effect persists in the absence of scanning and does not depend on initiator tRNA and eIF2. The results suggest that the initiation factors are not involved in the coupling mechanism.
[Mh] Termos MeSH primário: RNA Mensageiro/metabolismo
[Mh] Termos MeSH secundário: Regiões 5' não Traduzidas
Sistema Livre de Células/metabolismo
Fator de Iniciação 2 em Eucariotos/antagonistas & inibidores
Fator de Iniciação 2 em Eucariotos/metabolismo
Fator de Iniciação 4A em Eucariotos/antagonistas & inibidores
Fator de Iniciação 4A em Eucariotos/metabolismo
Genes Reporter
Sítios Internos de Entrada Ribossomal/genética
Iniciação Traducional da Cadeia Peptídica
Terminação Traducional da Cadeia Peptídica
Plasmídeos/metabolismo
Esteróis/química
Esteróis/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (5' Untranslated Regions); 0 (Eukaryotic Initiation Factor-2); 0 (Internal Ribosome Entry Sites); 0 (RNA, Messenger); 0 (Sterols); 0 (hippuristanol); EC 2.7.7.- (Eukaryotic Initiation Factor-4A)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170919
[St] Status:MEDLINE
[do] DOI:10.1134/S0006297917070069


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[PMID]:28911096
[Au] Autor:Li W; Li W; Laishram RS; Hoque M; Ji Z; Tian B; Anderson RA
[Ad] Endereço:University of Wisconsin-Madison, School of Medicine and Public Health, Madison, WI 53706, USA.
[Ti] Título:Distinct regulation of alternative polyadenylation and gene expression by nuclear poly(A) polymerases.
[So] Source:Nucleic Acids Res;45(15):8930-8942, 2017 Sep 06.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Polyadenylation of nascent RNA by poly(A) polymerase (PAP) is important for 3' end maturation of almost all eukaryotic mRNAs. Most mammalian genes harbor multiple polyadenylation sites (PASs), leading to expression of alternative polyadenylation (APA) isoforms with distinct functions. How poly(A) polymerases may regulate PAS usage and hence gene expression is poorly understood. Here, we show that the nuclear canonical (PAPα and PAPγ) and non-canonical (Star-PAP) PAPs play diverse roles in PAS selection and gene expression. Deficiencies in the PAPs resulted in perturbations of gene expression, with Star-PAP impacting lowly expressed mRNAs and long-noncoding RNAs to the greatest extent. Importantly, different PASs of a gene are distinctly regulated by different PAPs, leading to widespread relative expression changes of APA isoforms. The location and surrounding sequence motifs of a PAS appear to differentiate its regulation by the PAPs. We show Star-PAP-specific PAS usage regulates the expression of the eukaryotic translation initiation factor EIF4A1, the tumor suppressor gene PTEN and the long non-coding RNA NEAT1. The Star-PAP-mediated APA of PTEN is essential for DNA damage-induced increase of PTEN protein levels. Together, our results reveal a PAS-guided and PAP-mediated paradigm for gene expression in response to cellular signaling cues.
[Mh] Termos MeSH primário: Fator de Iniciação 4A em Eucariotos/genética
Regulação da Expressão Gênica
PTEN Fosfo-Hidrolase/genética
Polinucleotídeo Adenililtransferase/genética
RNA Longo não Codificante/genética
[Mh] Termos MeSH secundário: Núcleo Celular/genética
Núcleo Celular/metabolismo
Fator de Iniciação 4A em Eucariotos/metabolismo
Perfilação da Expressão Gênica
Células HEK293
Seres Humanos
Isoenzimas/antagonistas & inibidores
Isoenzimas/genética
Isoenzimas/metabolismo
Cinética
PTEN Fosfo-Hidrolase/metabolismo
Poliadenilação
Polinucleotídeo Adenililtransferase/antagonistas & inibidores
Polinucleotídeo Adenililtransferase/metabolismo
RNA Longo não Codificante/metabolismo
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
RNA Interferente Pequeno/genética
RNA Interferente Pequeno/metabolismo
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Isoenzymes); 0 (NEAT1 long non-coding RNA, human); 0 (RNA, Long Noncoding); 0 (RNA, Messenger); 0 (RNA, Small Interfering); EC 2.7.7.- (Eukaryotic Initiation Factor-4A); EC 2.7.7.19 (Polynucleotide Adenylyltransferase); EC 2.7.7.19 (Star-PAP protein, human); EC 3.1.3.67 (PTEN Phosphohydrolase); EC 3.1.3.67 (PTEN protein, human)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171012
[Lr] Data última revisão:
171012
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170916
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx560


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[PMID]:28757063
[Au] Autor:Tillotson J; Kedzior M; Guimarães L; Ross AB; Peters TL; Ambrose AJ; Schmidlin CJ; Zhang DD; Costa-Lotufo LV; Rodríguez AD; Schatz JH; Chapman E
[Ad] Endereço:Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, 1703 East Mabel Street, P.O. Box 210207, Tuscon, AZ 85721, United States.
[Ti] Título:ATP-competitive, marine derived natural products that target the DEAD box helicase, eIF4A.
[So] Source:Bioorg Med Chem Lett;27(17):4082-4085, 2017 09 01.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Activation of translation initiation is a common trait of cancer cells. Formation of the heterotrimeric eukaryotic initiation factor F (eIF4F) complex is the rate-limiting step in 5' m7GpppN cap-dependent translation. This trimeric complex includes the eIF4E cap binding protein, the eIF4G scaffolding protein, and the DEAD box RNA helicase eIF4A. eIF4A is an ATP-dependent helicase and because it is the only enzyme in the eIF4F complex, it has been shown to be a potential therapeutic target for a variety of malignancies. To this end, we have used a simple ATPase biochemical screen to survey several hundred marine and terrestrial derived natural products. Herein, we report the discovery of two natural products from marine sources, elisabatin A (1) and allolaurinterol (2), which show low µM inhibition of eIF4A ATPase activity. Enzymological analyses revealed 1 and 2 to be ATP-competitive, and cellular evaluations showed reasonable cytotoxicity against A549 (lung cancer) and MDA-MA-468 (breast cancer) cell lines. However, only compound 2 showed potent inhibition of helicase activity congruent with its ATPase inhibitory activity.
[Mh] Termos MeSH primário: Trifosfato de Adenosina/metabolismo
Produtos Biológicos/farmacologia
Inibidores Enzimáticos/farmacologia
Fator de Iniciação 4A em Eucariotos/antagonistas & inibidores
[Mh] Termos MeSH secundário: Produtos Biológicos/química
Produtos Biológicos/isolamento & purificação
Linhagem Celular Tumoral
Sobrevivência Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Inibidores Enzimáticos/química
Inibidores Enzimáticos/isolamento & purificação
Fator de Iniciação 4A em Eucariotos/metabolismo
Seres Humanos
Estrutura Molecular
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Biological Products); 0 (Enzyme Inhibitors); 8L70Q75FXE (Adenosine Triphosphate); EC 2.7.7.- (Eukaryotic Initiation Factor-4A)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171125
[Lr] Data última revisão:
171125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170801
[St] Status:MEDLINE


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[PMID]:28671258
[Au] Autor:Auler PA; Benitez LC; do Amaral MN; Vighi IL; Rodrigues GS; da Maia LC; Braga EJB
[Ad] Endereço:Departamento de Botânica, Instituto de Biologia, , , Brasil pri_auler@hotmail.com.
[Ti] Título:Selection of candidate reference genes and validation for real-time PCR studies in rice plants exposed to low temperatures.
[So] Source:Genet Mol Res;16(2), 2017 Jun 29.
[Is] ISSN:1676-5680
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:Rice is a cereal that presents a great ability to adapt to different soil and climate conditions. However, as it is a tropical crop with C3 metabolism, it performs better in warm temperatures with high solar radiation. Tolerance to stress caused by low temperatures is a highly complex process that involves various metabolic pathways and cellular compartments, resulting in general or specific effects on plant growth and development. In order to observe the true effect of a particular stress on genetic expression, reference genes need to be chosen for real-time PCRs, the expression levels of which should remain stable independent of the situation imposed. In this paper, the expression stability was evaluated of the actin 11 (ACT11), ubiquitin-conjugating enzyme 2 (UBC-E2), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), beta tubilin (ß-Tubulin), eukaryotic initiation factor 4α (eIF-4-α), eukaryotic initiation factor 1α (eIF-1-α), ubiquitin 10 (UBQ10), ubiquitin 5 (UBQ5), aquaporin (TIP41), and cyclophilin genes, in two rice genotypes cultivated in low temperature (13°C) conditions in vegetative stage (V4). The analysis material (leaves) was collected after 0, 6, 24, 48, and 72 h of exposure to the stress. In this study, the geNorm, BestKeeper, ΔCt, NormFinder, and RefFinder methods were used to evaluate the expression stability of the candidate reference genes. The results revealed that the most indicated genes for all the analysis methods were UBQ10 and UBQ5 for BRS Bojuru and BRS Pampa, respectively. On the other hand, the eIF-1-α gene presents the least expression stability and is not indicated for studies of rice plants subjected to low temperatures. The validation with the antioxidant system genes SODCc1-Cu/Zn, CATC, APX2, and GR2 confirmed the importance of using previously tested normalizing genes for adequate real-time PCR results.
[Mh] Termos MeSH primário: Resposta ao Choque Frio/genética
Genes de Plantas
Oryza/genética
Reação em Cadeia da Polimerase em Tempo Real/normas
[Mh] Termos MeSH secundário: Actinas/genética
Aquaporinas/genética
Ciclofilinas/genética
Fator de Iniciação 4A em Eucariotos/genética
Gliceraldeído-3-Fosfato Desidrogenase (Fosforiladora)/genética
Proteínas de Plantas/genética
Reação em Cadeia da Polimerase em Tempo Real/métodos
Padrões de Referência
Tubulina (Proteína)/genética
Ubiquitinas/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; VALIDATION STUDIES
[Nm] Nome de substância:
0 (Actins); 0 (Aquaporins); 0 (Plant Proteins); 0 (Tubulin); 0 (Ubiquitins); EC 1.2.1.12 (Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)); EC 2.7.7.- (Eukaryotic Initiation Factor-4A); EC 5.2.1.- (Cyclophilins)
[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:170704
[St] Status:MEDLINE
[do] DOI:10.4238/gmr16029695


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[PMID]:28358513
[Au] Autor:Ito M; Tanaka T; Cary DR; Iwatani-Yoshihara M; Kamada Y; Kawamoto T; Aparicio S; Nakanishi A; Imaeda Y
[Ad] Endereço:Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited , 26-1, Muraoka-Higashi 2-Chome, Fujisawa, Kanagawa 251-8555, Japan.
[Ti] Título:Discovery of Novel 1,4-Diacylpiperazines as Selective and Cell-Active eIF4A3 Inhibitors.
[So] Source:J Med Chem;60(8):3335-3351, 2017 Apr 27.
[Is] ISSN:1520-4804
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Eukaryotic initiation factor 4A3 (eIF4A3), a member of the DEAD-box RNA helicase family, is one of the core components of the exon junction complex (EJC). The EJC is known to be involved in a variety of RNA metabolic processes typified by nonsense-mediated RNA decay (NMD). In order to identify molecular probes to investigate the functions and therapeutic relevance of eIF4A3, a search for selective eIF4A3 inhibitors was conducted. Through the chemical optimization of 1,4-diacylpiperazine derivatives identified via high-throughput screening (HTS), we discovered the first reported selective eIF4A3 inhibitor 53a exhibiting cellular NMD inhibitory activity. A surface plasmon resonance (SPR) biosensing assay ascertained the direct binding of 53a and its analog 52a to eIF4A3 and revealed that the binding occurs at a non-ATP binding site. Compounds 52a and 53a represent novel molecular probes for further study of eIF4A3, the EJC, and NMD.
[Mh] Termos MeSH primário: RNA Helicases DEAD-box/antagonistas & inibidores
Fator de Iniciação 4A em Eucariotos/antagonistas & inibidores
Piperazinas/farmacologia
[Mh] Termos MeSH secundário: Adenosina Trifosfatases/antagonistas & inibidores
Descoberta de Drogas
Células HEK293
Seres Humanos
Espectrometria de Massas
Piperazinas/química
Espectroscopia de Prótons por Ressonância Magnética
Relação Estrutura-Atividade
Ressonância de Plasmônio de Superfície
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Piperazines); EC 2.7.7.- (Eukaryotic Initiation Factor-4A); EC 3.6.1.- (Adenosine Triphosphatases); EC 3.6.1.- (EIF4A3 protein, human); EC 3.6.4.13 (DEAD-box RNA Helicases)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170620
[Lr] Data última revisão:
170620
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170331
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jmedchem.6b01904


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[PMID]:28334780
[Au] Autor:Miller EE; Kobayashi GS; Musso CM; Allen M; Ishiy FAA; de Caires LC; Goulart E; Griesi-Oliveira K; Zechi-Ceide RM; Richieri-Costa A; Bertola DR; Passos-Bueno MR; Silver DL
[Ad] Endereço:Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC, USA.
[Ti] Título:EIF4A3 deficient human iPSCs and mouse models demonstrate neural crest defects that underlie Richieri-Costa-Pereira syndrome.
[So] Source:Hum Mol Genet;26(12):2177-2191, 2017 Jun 15.
[Is] ISSN:1460-2083
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Biallelic loss-of-function mutations in the RNA-binding protein EIF4A3 cause Richieri-Costa-Pereira syndrome (RCPS), an autosomal recessive condition mainly characterized by craniofacial and limb malformations. However, the pathogenic cellular mechanisms responsible for this syndrome are entirely unknown. Here, we used two complementary approaches, patient-derived induced pluripotent stem cells (iPSCs) and conditional Eif4a3 mouse models, to demonstrate that defective neural crest cell (NCC) development explains RCPS craniofacial abnormalities. RCPS iNCCs have decreased migratory capacity, a distinct phenotype relative to other craniofacial disorders. Eif4a3 haploinsufficient embryos presented altered mandibular process fusion and micrognathia, thus recapitulating the most penetrant phenotypes of the syndrome. These defects were evident in either ubiquitous or NCC-specific Eif4a3 haploinsufficient animals, demonstrating an autonomous requirement of Eif4a3 in NCCs. Notably, RCPS NCC-derived mesenchymal stem-like cells (nMSCs) showed premature bone differentiation, a phenotype paralleled by premature clavicle ossification in Eif4a3 haploinsufficient embryos. Likewise, nMSCs presented compromised in vitro chondrogenesis, and Meckel's cartilage was underdeveloped in vivo. These findings indicate novel and essential requirements of EIF4A3 for NCC migration and osteochondrogenic differentiation during craniofacial development. Altogether, complementary use of iPSCs and mouse models pinpoint unique cellular mechanisms by which EIF4A3 mutation causes RCPS, and provide a paradigm to study craniofacial disorders.
[Mh] Termos MeSH primário: Pé Torto Equinovaro/genética
RNA Helicases DEAD-box/genética
RNA Helicases DEAD-box/metabolismo
Fator de Iniciação 4A em Eucariotos/genética
Fator de Iniciação 4A em Eucariotos/metabolismo
Deformidades Congênitas da Mão/genética
Síndrome de Pierre Robin/genética
[Mh] Termos MeSH secundário: Animais
Osso e Ossos/metabolismo
Região Branquial/metabolismo
Diferenciação Celular/genética
Movimento Celular
Condrogênese/genética
Pé Torto Equinovaro/metabolismo
Anormalidades Craniofaciais/genética
Anormalidades Craniofaciais/metabolismo
Modelos Animais de Doenças
Deformidades Congênitas da Mão/metabolismo
Seres Humanos
Células-Tronco Pluripotentes Induzidas/metabolismo
Camundongos
Crista Neural/crescimento & desenvolvimento
Crista Neural/metabolismo
Osteogênese/genética
Síndrome de Pierre Robin/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 2.7.7.- (Eukaryotic Initiation Factor-4A); EC 3.6.1.- (EIF4A3 protein, human); EC 3.6.4.13 (DEAD-box RNA Helicases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171012
[Lr] Data última revisão:
171012
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170324
[St] Status:MEDLINE
[do] DOI:10.1093/hmg/ddx078


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[PMID]:28283335
[Au] Autor:Ito M; Iwatani M; Kamada Y; Sogabe S; Nakao S; Tanaka T; Kawamoto T; Aparicio S; Nakanishi A; Imaeda Y
[Ad] Endereço:Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan. Electronic address: masahiro.ito@takeda.com.
[Ti] Título:Discovery of selective ATP-competitive eIF4A3 inhibitors.
[So] Source:Bioorg Med Chem;25(7):2200-2209, 2017 Apr 01.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Eukaryotic initiation factor 4A3 (eIF4A3), an ATP-dependent RNA helicase, is a core component of exon junction complex (EJC). EJC has a variety of roles in RNA metabolism such as translation, surveillance, and localization of spliced RNA. It is worthwhile to identify selective eIF4A3 inhibitors with a view to investigating the functions of eIF4A3 and EJC further to clarify the roles of the ATPase and helicase activities in cells. Our chemical optimization of hit compound 2 culminated in the discovery of ATP-competitive eIF4A3 inhibitor 18 with submicromolar ATPase inhibitory activity and excellent selectivity over other helicases. Hence, compound 18 could be a valuable chemical probe to elucidate the detailed functions of eIF4A3 and EJC.
[Mh] Termos MeSH primário: Trifosfato de Adenosina/metabolismo
RNA Helicases DEAD-box/antagonistas & inibidores
Inibidores Enzimáticos/farmacologia
Fator de Iniciação 4A em Eucariotos/antagonistas & inibidores
[Mh] Termos MeSH secundário: Cromatografia Líquida de Alta Pressão
Cromatografia em Camada Delgada
Descoberta de Drogas
Inibidores Enzimáticos/química
Ensaios de Triagem em Larga Escala
História Medieval
Espectroscopia de Prótons por Ressonância Magnética
Espectrometria de Massas por Ionização por Electrospray
[Pt] Tipo de publicação:HISTORICAL ARTICLE; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 8L70Q75FXE (Adenosine Triphosphate); EC 2.7.7.- (Eukaryotic Initiation Factor-4A); EC 3.6.1.- (EIF4A3 protein, human); EC 3.6.4.13 (DEAD-box RNA Helicases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170312
[St] Status:MEDLINE


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[PMID]:28273136
[Au] Autor:Shadle SC; Zhong JW; Campbell AE; Conerly ML; Jagannathan S; Wong CJ; Morello TD; van der Maarel SM; Tapscott SJ
[Ad] Endereço:Molecular and Cellular Biology Program, University of Washington, Seattle, Washington, United States of America.
[Ti] Título:DUX4-induced dsRNA and MYC mRNA stabilization activate apoptotic pathways in human cell models of facioscapulohumeral dystrophy.
[So] Source:PLoS Genet;13(3):e1006658, 2017 Mar.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Facioscapulohumeral dystrophy (FSHD) is caused by the mis-expression of DUX4 in skeletal muscle cells. DUX4 is a transcription factor that activates genes normally associated with stem cell biology and its mis-expression in FSHD cells results in apoptosis. To identify genes and pathways necessary for DUX4-mediated apoptosis, we performed an siRNA screen in an RD rhabdomyosarcoma cell line with an inducible DUX4 transgene. Our screen identified components of the MYC-mediated apoptotic pathway and the double-stranded RNA (dsRNA) innate immune response pathway as mediators of DUX4-induced apoptosis. Further investigation revealed that DUX4 expression led to increased MYC mRNA, accumulation of nuclear dsRNA foci, and activation of the dsRNA response pathway in both RD cells and human myoblasts. Nuclear dsRNA foci were associated with aggregation of the exon junction complex component EIF4A3. The elevation of MYC mRNA, dsRNA accumulation, and EIF4A3 nuclear aggregates in FSHD muscle cells suggest that these processes might contribute to FSHD pathophysiology.
[Mh] Termos MeSH primário: Apoptose
Proteínas de Homeodomínio/genética
Distrofia Muscular Facioescapuloumeral/genética
Distrofia Muscular Facioescapuloumeral/patologia
Proteínas Proto-Oncogênicas c-myc/genética
RNA de Cadeia Dupla/genética
Rabdomiossarcoma/genética
[Mh] Termos MeSH secundário: Caspases/metabolismo
Morte Celular
Linhagem Celular
Sobrevivência Celular
RNA Helicases DEAD-box/genética
Fator de Iniciação 4A em Eucariotos/genética
Éxons
Regulação da Expressão Gênica
Seres Humanos
Imunidade Inata
Mutação
Mioblastos/metabolismo
RNA de Cadeia Dupla/metabolismo
RNA Mensageiro/metabolismo
RNA Interferente Pequeno/metabolismo
Proteína Supressora de Tumor p53/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DUX4 protein, human); 0 (Homeodomain Proteins); 0 (MYC protein, human); 0 (Proto-Oncogene Proteins c-myc); 0 (RNA, Double-Stranded); 0 (RNA, Messenger); 0 (RNA, Small Interfering); 0 (TP53 protein, human); 0 (Tumor Suppressor Protein p53); EC 2.7.7.- (Eukaryotic Initiation Factor-4A); EC 3.4.22.- (Caspases); EC 3.6.1.- (EIF4A3 protein, human); EC 3.6.4.13 (DEAD-box RNA Helicases)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171005
[Lr] Data última revisão:
171005
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170309
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1006658


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[PMID]:28242763
[Au] Autor:Zhao P; Liu Q; Miller WA; Goss DJ
[Ad] Endereço:From the Biochemistry and Chemistry Graduate Programs, Graduate Center, and.
[Ti] Título:Eukaryotic translation initiation factor 4G (eIF4G) coordinates interactions with eIF4A, eIF4B, and eIF4E in binding and translation of the barley yellow dwarf virus 3' cap-independent translation element (BTE).
[So] Source:J Biol Chem;292(14):5921-5931, 2017 Apr 07.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Barley yellow dwarf virus RNA, lacking a 5' cap and a 3' poly(A) tail, contains a cap-independent translation element (BTE) in the 3'-untranslated region that interacts with host translation initiation factor eIF4G. To determine how eIF4G recruits the mRNA, three eIF4G deletion mutants were constructed: (i) eIF4G601-1196, containing amino acids 601-1196, including the putative BTE-binding region, and binding domains for eIF4E, eIF4A, and eIF4B; (ii) eIF4G601-1488, which contains an additional C-terminal eIF4A-binding domain; and (iii) eIF4G742-1196, which lacks the eIF4E-binding site. eIF4G601-1196 binds BTE tightly and supports efficient translation. The helicase complex, consisting of eIF4A, eIF4B, and ATP, stimulated BTE binding with eIF4G601-1196 but not eIF4G601-1488, suggesting that the eIF4A binding domains may serve a regulatory role, with the C-terminal binding site having negative effects. eIF4E binding to eIF4G601-1196 induced a conformational change, significantly increasing the binding affinity to BTE. A comparison of the binding of eIF4G deletion mutants with BTEs containing mutations showed a general correlation between binding affinity and ability to facilitate translation. In summary, these results reveal a new role for the helicase complex in 3' cap-independent translation element-mediated translation and show that the functional core domain of eIF4G plus an adjacent probable RNA-binding domain mediate translation initiation.
[Mh] Termos MeSH primário: Fator de Iniciação 4A em Eucariotos/metabolismo
Fator de Iniciação 4E em Eucariotos/metabolismo
Fator de Iniciação 4G em Eucariotos/metabolismo
Fatores de Iniciação em Eucariotos/metabolismo
Luteovirus/metabolismo
Biossíntese de Proteínas/fisiologia
RNA Helicases/metabolismo
RNA Viral/metabolismo
Proteínas Virais/biossíntese
[Mh] Termos MeSH secundário: Fator de Iniciação 4A em Eucariotos/genética
Fator de Iniciação 4E em Eucariotos/genética
Fator de Iniciação 4G em Eucariotos/genética
Fatores de Iniciação em Eucariotos/genética
Luteovirus/genética
RNA Helicases/genética
RNA Viral/genética
Proteínas Virais/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Eukaryotic Initiation Factor-4E); 0 (Eukaryotic Initiation Factor-4G); 0 (Eukaryotic Initiation Factors); 0 (RNA, Viral); 0 (Viral Proteins); 0 (eIF-4B); EC 2.7.7.- (Eukaryotic Initiation Factor-4A); EC 3.6.4.13 (RNA Helicases)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170601
[Lr] Data última revisão:
170601
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170301
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M116.764902


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[PMID]:28122908
[Au] Autor:Cai W; Chen ZX; Rane G; Singh SS; Choo Z; Wang C; Yuan Y; Tan TZ; Arfuso F; Yap CT; Pongor LS; Yang H; Lee MB; Goh BC; Sethi G; Benoukraf T; Tergaonkar V; Kumar AP
[Ad] Endereço:Cancer Science Institute of Singapore, National University of Singapore, Singapore.
[Ti] Título:Wanted DEAD/H or Alive: Helicases Winding Up in Cancers.
[So] Source:J Natl Cancer Inst;109(6), 2017 01.
[Is] ISSN:1460-2105
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cancer is one of the most studied areas of human biology over the past century. Despite having attracted much attention, hype, and investments, the search to find a cure for cancer remains an uphill battle. Recent discoveries that challenged the central dogma of molecular biology not only further increase the complexity but also demonstrate how various types of noncoding RNAs such as microRNA and long noncoding RNA, as well as their related processes such as RNA editing, are important in regulating gene expression. Parallel to this aspect, an increasing number of reports have focused on a family of proteins known as DEAD/H-box helicases involved in RNA metabolism, regulation of long and short noncoding RNAs, and novel roles as "editing helicases" and their association with cancers. This review summarizes recent findings on the roles of RNA helicases in various cancers, which are broadly classified into adult solid tumors, childhood solid tumors, leukemia, and cancer stem cells. The potential small molecule inhibitors of helicases and their therapeutic value are also discussed. In addition, analyzing next-generation sequencing data obtained from public portals and reviewing existing literature, we provide new insights on the potential of DEAD/H-box helicases to act as pharmacological drug targets in cancers.
[Mh] Termos MeSH primário: RNA Helicases DEAD-box/antagonistas & inibidores
RNA Helicases DEAD-box/metabolismo
Inibidores Enzimáticos/uso terapêutico
Neoplasias/tratamento farmacológico
Neoplasias/enzimologia
[Mh] Termos MeSH secundário: RNA Helicases DEAD-box/genética
Fator de Iniciação 4A em Eucariotos/antagonistas & inibidores
Seres Humanos
Neoplasias/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Enzyme Inhibitors); EC 2.7.7.- (Eukaryotic Initiation Factor-4A); EC 3.6.1.- (DDX3X protein, human); EC 3.6.1.- (Ddx5 protein, human); EC 3.6.4.13 (DEAD-box RNA Helicases)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170127
[St] Status:MEDLINE



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