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  1 / 19057 MEDLINE  
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[PMID]:29259037
[Au] Autor:Falch CM; Sundaram AYM; Øystese KA; Normann KR; Lekva T; Silamikelis I; Eieland AK; Andersen M; Bollerslev J; Olarescu NC
[Ad] Endereço:Section of Specialized EndocrinologyDepartment of Endocrinology cafal14@student.sdu.dk.
[Ti] Título:Gene expression profiling of fast- and slow-growing non-functioning gonadotroph pituitary adenomas.
[So] Source:Eur J Endocrinol;178(3):295-307, 2018 Mar.
[Is] ISSN:1479-683X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Reliable biomarkers associated with aggressiveness of non-functioning gonadotroph adenomas (GAs) are lacking. As the growth of tumor remnants is highly variable, molecular markers for growth potential prediction are necessary. We hypothesized that fast- and slow-growing GAs present different gene expression profiles and reliable biomarkers for tumor growth potential could be identified, focusing on the specific role of epithelial-mesenchymal transition (EMT). DESIGN AND METHODS: Eight GAs selected for RNA sequencing were equally divided into fast- and slow-growing group by the tumor volume doubling time (TVDT) median (27.75 months). Data were analyzed by tophat2, cufflinks and cummeRbund pipeline. 40 genes were selected for RT-qPCR validation in 20 GAs based on significance, fold-change and pathway analyses. The effect of silencing (metadherin) and (endomucin) on migration of human adenoma cells was evaluated. RESULTS: 350 genes were significantly differentially expressed (282 genes upregulated and 68 downregulated in the fast group, -adjusted <0.05). Among 40 selected genes, 11 showed associations with TVDT (-0.669< <-0.46, < 0.05). These were and six EMT-related genes ( and ). , but not , demonstrated involvement in cell migration and association with EMT markers. CONCLUSIONS: Fast- and slow-growing GAs present different gene expression profiles, and genes related to EMT have higher expression in fast-growing tumors. In addition to , identified as an important contributor to aggressiveness, the other genes might represent markers for tumor growth potential and possible targets for drug therapy.
[Mh] Termos MeSH primário: Adenoma/genética
Transição Epitelial-Mesenquimal/genética
Neoplasias Hipofisárias/genética
RNA Mensageiro/metabolismo
[Mh] Termos MeSH secundário: Proteínas Adaptadoras de Transdução de Sinal/genética
Adenoma/metabolismo
Adulto
Idoso
Caderinas/genética
Moléculas de Adesão Celular/genética
Movimento Celular/genética
Subunidades Catalíticas da Proteína Quinase Dependente de AMP Cíclico/genética
Feminino
Hormônio Foliculoestimulante/metabolismo
Perfilação da Expressão Gênica
Regulação Neoplásica da Expressão Gênica
Inativação Gênica
Seres Humanos
Técnicas In Vitro
Peptídeos e Proteínas de Sinalização Intracelular/genética
Hormônio Luteinizante/metabolismo
Masculino
Glicoproteínas de Membrana/genética
Proteínas Associadas aos Microtúbulos/genética
Meia-Idade
Miosina Tipo I/genética
Proteínas do Tecido Nervoso/genética
Neoplasias Hipofisárias/metabolismo
Proteínas Proto-Oncogênicas/genética
Receptores de Superfície Celular/genética
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Ribonucleases/genética
Sialoglicoproteínas/genética
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adaptor Proteins, Signal Transducing); 0 (Cadherins); 0 (Cell Adhesion Molecules); 0 (EMCN protein, human); 0 (GPM6A protein, human); 0 (Intracellular Signaling Peptides and Proteins); 0 (MTDH protein, human); 0 (MYO1B protein, human); 0 (Membrane Glycoproteins); 0 (Microtubule-Associated Proteins); 0 (Nerve Tissue Proteins); 0 (PCDH18 protein, human); 0 (Proto-Oncogene Proteins); 0 (RNA, Messenger); 0 (Receptors, Cell Surface); 0 (SKIL protein, human); 0 (SPAG9 protein, human); 0 (Sialoglycoproteins); 0 (UNC5H4 protein, human); 0 (hook1 protein, human); 9002-67-9 (Luteinizing Hormone); 9002-68-0 (Follicle Stimulating Hormone); EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinase Catalytic Subunits); EC 2.7.11.11 (PRKACB protein, human); EC 3.1.- (CNOT6L protein, human); EC 3.1.- (Ribonucleases); EC 3.6.1.- (Myosin Type I)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171221
[St] Status:MEDLINE
[do] DOI:10.1530/EJE-17-0702


  2 / 19057 MEDLINE  
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[PMID]:29298350
[Au] Autor:Tatsuta T; Satoh T; Sugawara S; Hara A; Hosono M
[Ad] Endereço:Division of Cell Recognition Study, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Aobaku, Sendai, Japan.
[Ti] Título:Sialic acid-binding lectin from bullfrog eggs inhibits human malignant mesothelioma cell growth in vitro and in vivo.
[So] Source:PLoS One;13(1):e0190653, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Malignant mesothelioma is an aggressive cancer that results from exposure to asbestos. The therapeutic options for this type of cancer are limited; therefore, the development of novel therapeutic agents is urgently required. Sialic acid-binding lectin isolated from Rana catesbeiana oocytes (cSBL) is a novel therapeutic candidate for cancer, which exhibits antitumor activity mediated through RNA degradation. In the present study, we evaluated the effect of cSBL in vitro and in vivo. Xenograft-competent H2452 and MSTO human mesothelioma cell lines were treated with cSBL, and the pathway by which cSBL induces apoptosis was analyzed. In vivo studies were performed using nude mice inoculated with one of the two cell lines, and the effects of cSBL and pemetrexed were monitored simultaneously. Furthermore, the pharmacological interactions between the three agents (pemetrexed, cisplatin and cSBL) were statistically assessed. It was demonstrated that cSBL treatments caused morphological and biochemical apoptotic changes in both cell lines. Caspase cascade analysis revealed that an intrinsic pathway mediated cSBL-induced apoptosis. The administration of cSBL significantly inhibited tumor growth in two xenograft models, without any adverse effects. Furthermore, the combination index and dose reduction index values indicated that the cSBL + pemetrexed combination showed the highest synergism, and thus potential for reducing dosage of each drug, compared with the other combinations, including the existing pemetrexed + cisplatin regimen. cSBL exerted prominent antitumor effects on malignant mesothelioma cells in vitro and in vivo, and showed favorable effects when combined with pemetrexed. These results suggest that cSBL has potential as a novel drug for the treatment of malignant mesothelioma.
[Mh] Termos MeSH primário: Proteínas de Anfíbios/farmacologia
Proliferação Celular/efeitos dos fármacos
Lectinas/farmacologia
Mesotelioma/patologia
Óvulo/química
Ribonucleases/farmacologia
[Mh] Termos MeSH secundário: Proteínas de Anfíbios/isolamento & purificação
Animais
Apoptose/efeitos dos fármacos
Linhagem Celular Tumoral
Sinergismo Farmacológico
Feminino
Seres Humanos
Técnicas In Vitro
Lectinas/isolamento & purificação
Masculino
Camundongos Endogâmicos BALB C
Camundongos Nus
Pemetrexede/administração & dosagem
Rana catesbeiana
Ribonucleases/isolamento & purificação
Perda de Peso/efeitos dos fármacos
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Amphibian Proteins); 0 (Lectins); 04Q9AIZ7NO (Pemetrexed); EC 3.1.- (Ribonucleases); EC 3.1.- (leczyme protein, Rana)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180104
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190653


  3 / 19057 MEDLINE  
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[PMID]:29242153
[Au] Autor:Raj R; Mitra S; Gopal B
[Ad] Endereço:Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India.
[Ti] Título:Characterization of Staphylococcus epidermidis Polynucleotide phosphorylase and its interactions with ribonucleases RNase J1 and RNase J2.
[So] Source:Biochem Biophys Res Commun;495(2):2078-2084, 2018 01 08.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Polynucleotide phosphorylase catalyzes both 3'-5' exoribonuclease and polyadenylation reactions. The crystal structure of Staphylococcus epidermidis PNPase revealed a bound phosphate in the PH2 domain of each protomer coordinated by three adjacent serine residues. Mutational analysis suggests that phosphate coordination by these serine residues is essential to maintain the catalytic center in an active conformation. We note that PNPase forms a complex with RNase J1 and RNase J2 without substantially altering either exo-ribonuclease or polyadenylation activity of this enzyme. This decoupling of catalytic activity from protein-protein interactions suggests that association of these endo- or exo-ribonucleases with PNPase could be more relevant for cellular localization or concerted targeting of structured RNA for recycling.
[Mh] Termos MeSH primário: Simulação de Acoplamento Molecular
Nucleotidiltransferases/química
Nucleotidiltransferases/ultraestrutura
Ribonucleases/química
Ribonucleases/ultraestrutura
Staphylococcus epidermidis/enzimologia
[Mh] Termos MeSH secundário: Sítios de Ligação
Ativação Enzimática
Estabilidade Enzimática
Modelos Químicos
Complexos Multienzimáticos
Ligação Proteica
Conformação Proteica
Relação Estrutura-Atividade
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Multienzyme Complexes); EC 2.7.7.- (Nucleotidyltransferases); EC 2.7.7.- (polynucleotide pyrophosphorylase); EC 3.1.- (Ribonucleases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180214
[Lr] Data última revisão:
180214
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171216
[St] Status:MEDLINE


  4 / 19057 MEDLINE  
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[PMID]:29223150
[Au] Autor:Filippova JA; Semenov DV; Juravlev ES; Komissarov AB; Richter VA; Stepanov GA
[Ad] Endereço:Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090, Russia. stepanovga@niboch.nsc.ru.
[Ti] Título:Modern Approaches for Identification of Modified Nucleotides in RNA.
[So] Source:Biochemistry (Mosc);82(11):1217-1233, 2017 Nov.
[Is] ISSN:1608-3040
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:This review considers approaches for detection of modified monomers in the RNA structure of living organisms. Recently, some data on dynamic alterations in the pool of modifications of the key RNA species that depend on external factors affecting the cells and physiological conditions of the whole organism have been accumulated. The recent studies have presented experimental data on relationship between the mechanisms of formation of modified/minor nucleotides of RNA in mammalian cells and the development of various pathologies. The development of novel methods for detection of chemical modifications of RNA nucleotides in the cells of living organisms and accumulation of knowledge on the contribution of modified monomers to metabolism and functioning of individual RNA species establish the basis for creation of novel diagnostic and therapeutic approaches. This review includes a short description of routine methods for determination of modified nucleotides in RNA and considers in detail modern approaches that enable not only detection but also quantitative assessment of the modification level of various nucleotides in individual RNA species.
[Mh] Termos MeSH primário: Nucleotídeos/química
Processamento Pós-Transcricional do RNA
RNA/genética
[Mh] Termos MeSH secundário: Animais
Técnicas de Química Analítica/instrumentação
Técnicas de Química Analítica/métodos
Cromatografia Líquida de Alta Pressão
Técnicas Genéticas
Seres Humanos
Espectrometria de Massas
Métodos
Nucleotídeos/análise
Transcrição Reversa
Ribonucleases/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Nucleotides); 63231-63-0 (RNA); EC 3.1.- (Ribonucleases)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180103
[Lr] Data última revisão:
180103
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171211
[St] Status:MEDLINE
[do] DOI:10.1134/S0006297917110013


  5 / 19057 MEDLINE  
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[PMID]:29030484
[Au] Autor:Rojas-Ríos P; Chartier A; Pierson S; Simonelig M
[Ad] Endereço:mRNA Regulation and Development, Institute of Human Genetics, UMR9002 CNRS-Université de Montpellier, Montpellier Cedex 5, France.
[Ti] Título:Aubergine and piRNAs promote germline stem cell self-renewal by repressing the proto-oncogene .
[So] Source:EMBO J;36(21):3194-3211, 2017 Nov 02.
[Is] ISSN:1460-2075
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:PIWI proteins play essential roles in germ cells and stem cell lineages. In , Piwi is required in somatic niche cells and germline stem cells (GSCs) to support GSC self-renewal and differentiation. Whether and how other PIWI proteins are involved in GSC biology remains unknown. Here, we show that Aubergine (Aub), another PIWI protein, is intrinsically required in GSCs for their self-renewal and differentiation. Aub needs to be loaded with piRNAs to control GSC self-renewal and acts through direct mRNA regulation. We identify the proto-oncogene, a regulator of mammalian hematopoietic stem cells, as a novel GSC differentiation factor. Aub stimulates GSC self-renewal by repressing mRNA translation and does so in part through recruitment of the CCR4-NOT complex. This study reveals the role of piRNAs and PIWI proteins in controlling stem cell homeostasis via translational repression and highlights piRNAs as major post-transcriptional regulators in key developmental decisions.
[Mh] Termos MeSH primário: Proteínas de Drosophila/genética
Drosophila melanogaster/genética
Células Germinativas/metabolismo
Fatores de Iniciação de Peptídeos/genética
Proteínas Proto-Oncogênicas c-cbl/genética
RNA Interferente Pequeno/genética
Células-Tronco/metabolismo
[Mh] Termos MeSH secundário: Animais
Proteínas Argonauta/genética
Proteínas Argonauta/metabolismo
Sequência de Bases
Proteínas de Transporte/genética
Proteínas de Transporte/metabolismo
Diferenciação Celular
Linhagem da Célula/genética
Proteínas de Drosophila/metabolismo
Drosophila melanogaster/crescimento & desenvolvimento
Drosophila melanogaster/metabolismo
Embrião não Mamífero
Regulação da Expressão Gênica no Desenvolvimento
Células Germinativas/crescimento & desenvolvimento
Fatores de Iniciação de Peptídeos/metabolismo
Proteínas Proto-Oncogênicas c-cbl/metabolismo
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
RNA Interferente Pequeno/metabolismo
Ribonucleases/genética
Ribonucleases/metabolismo
Células-Tronco/citologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Argonaute Proteins); 0 (Carrier Proteins); 0 (Drosophila Proteins); 0 (NOT1 protein, Drosophila); 0 (Peptide Initiation Factors); 0 (RNA, Messenger); 0 (RNA, Small Interfering); 0 (aubergine protein, Drosophila); 0 (piwi protein, Drosophila); EC 2.3.2.27 (Proto-Oncogene Proteins c-cbl); EC 3.1.- (CCR4 protein, Drosophila); EC 3.1.- (Ribonucleases); EC 6.3.2.- (Cbl protein, Drosophila)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171109
[Lr] Data última revisão:
171109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171015
[St] Status:MEDLINE
[do] DOI:10.15252/embj.201797259


  6 / 19057 MEDLINE  
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[PMID]:28716897
[Au] Autor:Marona P; Górka J; Mazurek Z; Wilk W; Rys J; Majka M; Jura J; Miekus K
[Ad] Endereço:Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
[Ti] Título:MCPIP1 Downregulation in Clear Cell Renal Cell Carcinoma Promotes Vascularization and Metastatic Progression.
[So] Source:Cancer Res;77(18):4905-4920, 2017 Sep 15.
[Is] ISSN:1538-7445
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer and it forms highly vascularized tumors. The monocyte endoribonuclease MCPIP1 negatively regulates inflammation by degrading mRNA encoding proinflammatory cytokines, such as IL6, IL1, and IL12. MCPIP1 is also a negative regulator of NFκB and AP1 activity and it influences a broad range of miRNA activities. Here we report that MCPIP1 protein levels are decreased during renal cancer progression. In patient-derived tumors and xenografts established in NOD-SCID or nude mice, low MCPIP1 levels correlated strongly with increased proliferation, tumor outgrowth, and vascularity. MCPIP1 activity regulated secretion of VEGF, IL8, and CXCL12 leading to chemotaxis of microvascular endothelial cells, phosphorylation of VE-cadherin, and increased vascular permeability. Mechanistic investigations showed that MCPIP1 regulated ccRCC cell motility, lung metastasis, and mesenchymal phenotype by regulating key elements in the EMT signaling axis. Overall, our results illuminate how MCPIP1 serves as a key nodal point in coordinating tumor growth, angiogenesis, and metastatic spread in ccRCC. .
[Mh] Termos MeSH primário: Biomarcadores Tumorais/metabolismo
Carcinoma de Células Renais/secundário
Movimento Celular
Neoplasias Renais/patologia
Neovascularização Patológica/patologia
Ribonucleases/antagonistas & inibidores
Fatores de Transcrição/antagonistas & inibidores
[Mh] Termos MeSH secundário: Animais
Apoptose
Carcinoma de Células Renais/irrigação sanguínea
Carcinoma de Células Renais/metabolismo
Ciclo Celular
Proliferação Celular
Progressão da Doença
Regulação para Baixo
Feminino
Seres Humanos
Inflamação
Neoplasias Renais/irrigação sanguínea
Neoplasias Renais/metabolismo
Camundongos
Camundongos Endogâmicos NOD
Camundongos SCID
Gradação de Tumores
Metástase Neoplásica
Estadiamento de Neoplasias
Neovascularização Patológica/metabolismo
Fosforilação
Prognóstico
Ribonucleases/metabolismo
Transdução de Sinais
Fatores de Transcrição/metabolismo
Células Tumorais Cultivadas
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (Transcription Factors); EC 3.1.- (Ribonucleases); EC 3.1.- (ZC3H12A protein, human)
[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:170719
[St] Status:MEDLINE
[do] DOI:10.1158/0008-5472.CAN-16-3190


  7 / 19057 MEDLINE  
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[PMID]:28641106
[Au] Autor:Schoch KM; Miller TM
[Ad] Endereço:Department of Neurology, Hope Center for Neurological Disorders, Washington University in St. Louis, St. Louis, MO 63110, USA.
[Ti] Título:Antisense Oligonucleotides: Translation from Mouse Models to Human Neurodegenerative Diseases.
[So] Source:Neuron;94(6):1056-1070, 2017 Jun 21.
[Is] ISSN:1097-4199
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Multiple neurodegenerative diseases are characterized by single-protein dysfunction and aggregation. Treatment strategies for these diseases have often targeted downstream pathways to ameliorate consequences of protein dysfunction; however, targeting the source of that dysfunction, the affected protein itself, seems most judicious to achieve a highly effective therapeutic outcome. Antisense oligonucleotides (ASOs) are small sequences of DNA able to target RNA transcripts, resulting in reduced or modified protein expression. ASOs are ideal candidates for the treatment of neurodegenerative diseases, given numerous advancements made to their chemical modifications and delivery methods. Successes achieved in both animal models and human clinical trials have proven ASOs both safe and effective. With proper considerations in mind regarding the human applicability of ASOs, we anticipate ongoing in vivo research and clinical trial development of ASOs for the treatment of neurodegenerative diseases.
[Mh] Termos MeSH primário: Doenças Neurodegenerativas/tratamento farmacológico
Oligonucleotídeos Antissenso/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Barreira Hematoencefálica/metabolismo
Encéfalo/efeitos dos fármacos
Encéfalo/metabolismo
Modelos Animais de Doenças
Avaliação Pré-Clínica de Medicamentos
Seres Humanos
Injeções Intraventriculares
Injeções Espinhais
Camundongos
Doenças Neurodegenerativas/metabolismo
Oligonucleotídeos Antissenso/farmacologia
RNA Mensageiro/efeitos dos fármacos
RNA Mensageiro/metabolismo
Ribonucleases/efeitos dos fármacos
Ribonucleases/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Oligonucleotides, Antisense); 0 (RNA, Messenger); EC 3.1.- (Ribonucleases)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170801
[Lr] Data última revisão:
170801
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170623
[St] Status:MEDLINE


  8 / 19057 MEDLINE  
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[PMID]:28620029
[Au] Autor:Lilley DMJ
[Ad] Endereço:Cancer Research UK Nucleic Acid Structure Research Group, MSI/WTB Complex, The University of Dundee, Dow Street, Dundee DD1 5EH, U.K. d.m.j.lilley@dundee.ac.uk.
[Ti] Título:How RNA acts as a nuclease: some mechanistic comparisons in the nucleolytic ribozymes.
[So] Source:Biochem Soc Trans;45(3):683-691, 2017 Jun 15.
[Is] ISSN:1470-8752
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Recent structural and mechanistic studies have shed considerable light on the catalytic mechanisms of nucleolytic ribozymes. The discovery of several new ribozymes in this class has now allowed comparisons to be made, and the beginnings of mechanistic groupings to emerge.
[Mh] Termos MeSH primário: RNA Catalítico/metabolismo
[Mh] Termos MeSH secundário: Biocatálise
Domínio Catalítico
Coenzimas
Eucariotos/enzimologia
Seres Humanos
Modelos Moleculares
Conformação de Ácido Nucleico
RNA Catalítico/química
RNA Catalítico/classificação
Ribonucleases/química
Ribonucleases/classificação
Ribonucleases/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Coenzymes); 0 (RNA, Catalytic); EC 3.1.- (Ribonucleases)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170807
[Lr] Data última revisão:
170807
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170617
[St] Status:MEDLINE
[do] DOI:10.1042/BST20160158


  9 / 19057 MEDLINE  
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[PMID]:28576656
[Au] Autor:Song H; Zhang J; Li D; Cooper AMW; Silver K; Li T; Liu X; Ma E; Zhu KY; Zhang J
[Ad] Endereço:Research Institute of Applied Biology, Shanxi University, Taiyuan, Shanxi 030006, China; College of Life Science, Shanxi University, Taiyuan, Shanxi 030006, China.
[Ti] Título:A double-stranded RNA degrading enzyme reduces the efficiency of oral RNA interference in migratory locust.
[So] Source:Insect Biochem Mol Biol;86:68-80, 2017 Jul.
[Is] ISSN:1879-0240
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Application of RNA interference (RNAi) for insect pest management is limited by variable efficiency of RNAi in different insect species. In Locusta migratoria, RNAi is highly efficient through injection of dsRNA, but oral delivery of dsRNA is much less effective. Efforts to understand this phenomenon have shown that dsRNA is more rapidly degraded in midgut fluid than in hemolymph due to nuclease enzyme activity. In the present study, we identified and characterized two full-length cDNAs of double-stranded RNA degrading enzymes (dsRNase) from midgut of L. migratoria, which were named LmdsRNase2 and LmdsRNase3. Gene expression analysis revealed that LmdsRNase2 and LmdsRNase3 were predominantly expressed in the midgut, relatively lower expression in gastric caeca, and trace expression in other tested tissues. Incubation of dsRNA in midgut fluid from LmdsRNase3-suppressed larvae or control larvae injected with dsGFP resulted in high levels of degradation; however, dsRNA incubated in midgut fluid from LmdsRNase2-suppressed larvae was more stable, indicating LmdsRNase2 is responsible for dsRNA degradation in the midgut. To verify the biological function of LmdsRNase2 in vivo, nymphs were injected with dsGFP, dsLmdsRNase2 or dsLmdsRNase3 and chitinase 10 (LmCht10) or chitin synthase 1 (LmCHS1) dsRNA were orally delivered. Mortality associated with reporter gene knockdown was observed only in locusts injected with dsLmdsRNase2 (48% and 22%, for dsLmCht10 and dsLmCHS1, respectively), implicating LmdsRNase2 in reducing RNAi efficiency. Furthermore, recombinantly expressed LmdsRNase2 fusion proteins degraded dsRNA rapidly, whereas LmdsRNase3 did not. These results suggest that rapid degradation of dsRNA by dsRNase2 in the midgut is an important factor causing low RNAi efficiency when dsRNA is orally delivered in the locust.
[Mh] Termos MeSH primário: Locusta migratoria/enzimologia
Interferência de RNA
RNA de Cadeia Dupla/metabolismo
Ribonucleases/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Proteínas de Insetos/metabolismo
Dados de Sequência Molecular
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Insect Proteins); 0 (RNA, Double-Stranded); EC 3.1.- (Ribonucleases)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170828
[Lr] Data última revisão:
170828
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170604
[St] Status:MEDLINE


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[PMID]:28575517
[Au] Autor:Matelska D; Steczkiewicz K; Ginalski K
[Ad] Endereço:University of Warsaw, CeNT, Laboratory of Bioinformatics and Systems Biology, Zwirki i Wigury 93, 02-089 Warsaw, Poland.
[Ti] Título:Comprehensive classification of the PIN domain-like superfamily.
[So] Source:Nucleic Acids Res;45(12):6995-7020, 2017 Jul 07.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:PIN-like domains constitute a widespread superfamily of nucleases, diverse in terms of the reaction mechanism, substrate specificity, biological function and taxonomic distribution. Proteins with PIN-like domains are involved in central cellular processes, such as DNA replication and repair, mRNA degradation, transcription regulation and ncRNA maturation. In this work, we identify and classify the most complete set of PIN-like domains to provide the first comprehensive analysis of sequence-structure-function relationships within the whole PIN domain-like superfamily. Transitive sequence searches using highly sensitive methods for remote homology detection led to the identification of several new families, including representatives of Pfam (DUF1308, DUF4935) and CDD (COG2454), and 23 other families not classified in the public domain databases. Further sequence clustering revealed relationships between individual sequence clusters and showed heterogeneity within some families, suggesting a possible functional divergence. With five structural groups, 70 defined clusters, over 100,000 proteins, and broad biological functions, the PIN domain-like superfamily constitutes one of the largest and most diverse nuclease superfamilies. Detailed analyses of sequences and structures, domain architectures, and genomic contexts allowed us to predict biological function of several new families, including new toxin-antitoxin components, proteins involved in tRNA/rRNA maturation and transcription/translation regulation.
[Mh] Termos MeSH primário: Desoxirribonucleases/química
Desoxirribonucleases/classificação
Ribonucleases/química
Ribonucleases/classificação
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Bactérias/enzimologia
Bactérias/genética
Bacteriófagos/enzimologia
Bacteriófagos/genética
Sítios de Ligação
Biocatálise
Cristalografia por Raios X
Desoxirribonucleases/genética
Desoxirribonucleases/metabolismo
Fungos/enzimologia
Fungos/genética
Seres Humanos
Cinética
Modelos Moleculares
Ligação Proteica
Conformação Proteica em alfa-Hélice
Conformação Proteica em Folha beta
Domínios Proteicos
Estrutura Terciária de Proteína
Ribonucleases/genética
Ribonucleases/metabolismo
Alinhamento de Sequência
Homologia de Sequência de Aminoácidos
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 3.1.- (Deoxyribonucleases); EC 3.1.- (Ribonucleases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171011
[Lr] Data última revisão:
171011
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170603
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx494



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