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Pesquisa : D12.776.624.664.520.750.470 [Categoria DeCS]
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  1 / 210 MEDLINE  
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[PMID]:26927155
[Au] Autor:Nakano K; Watanabe T
[Ad] Endereço:Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 4-6-1, Shirokanedai, Minatoku, Tokyo 108-8639, Japan. nakanokz@ims.u-tokyo.ac.jp.
[Ti] Título:HTLV-1 Rex Tunes the Cellular Environment Favorable for Viral Replication.
[So] Source:Viruses;8(3):58, 2016 Feb 24.
[Is] ISSN:1999-4915
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Human T-cell leukemia virus type-1 (HTLV-1) Rex is a viral RNA binding protein. The most important and well-known function of Rex is stabilizing and exporting viral mRNAs from the nucleus, particularly for unspliced/partially-spliced mRNAs encoding the structural proteins essential for viral replication. Without Rex, these unspliced viral mRNAs would otherwise be completely spliced. Therefore, Rex is vital for the translation of structural proteins and the stabilization of viral genomic RNA and, thus, for viral replication. Rex schedules the period of extensive viral replication and suppression to enter latency. Although the importance of Rex in the viral life-cycle is well understood, the underlying molecular mechanism of how Rex achieves its function has not been clarified. For example, how does Rex protect unspliced/partially-spliced viral mRNAs from the host cellular splicing machinery? How does Rex protect viral mRNAs, antigenic to eukaryotic cells, from cellular mRNA surveillance mechanisms? Here we will discuss these mechanisms, which explain the function of Rex as an organizer of HTLV-1 expression based on previously and recently discovered aspects of Rex. We also focus on the potential influence of Rex on the homeostasis of the infected cell and how it can exert its function.
[Mh] Termos MeSH primário: Regulação Viral da Expressão Gênica
Produtos do Gene rex/metabolismo
Interações Hospedeiro-Patógeno
Vírus 1 Linfotrópico T Humano/fisiologia
Replicação Viral
[Mh] Termos MeSH secundário: Seres Humanos
Biossíntese de Proteínas
Processamento de RNA
RNA Viral/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Gene Products, rex); 0 (RNA, Viral); 0 (rex Protein, Human T-lymphotropic virus 1)
[Em] Mês de entrada:1611
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160302
[St] Status:MEDLINE


  2 / 210 MEDLINE  
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[PMID]:26581997
[Au] Autor:Cavallari I; Rende F; Bona MK; Sztuba-Solinska J; Silic-Benussi M; Tognon M; LeGrice SF; Franchini G; D'Agostino DM; Ciminale V
[Ad] Endereço:Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.
[Ti] Título:Expression of Alternatively Spliced Human T-Cell Leukemia Virus Type 1 mRNAs Is Influenced by Mitosis and by a Novel cis-Acting Regulatory Sequence.
[So] Source:J Virol;90(3):1486-98, 2015 Nov 18.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:UNLABELLED: Human T-cell leukemia virus type 1 (HTLV-1) expression depends on the concerted action of Tax, which drives transcription of the viral genome, and Rex, which favors expression of incompletely spliced mRNAs and determines a 2-phase temporal pattern of viral expression. In the present study, we investigated the Rex dependence of the complete set of alternatively spliced HTLV-1 mRNAs. Analyses of cells transfected with Rex-wild-type and Rex-knockout HTLV-1 molecular clones using splice site-specific quantitative reverse transcription (qRT)-PCR revealed that mRNAs encoding the p30Tof, p13, and p12/8 proteins were Rex dependent, while the p21rex mRNA was Rex independent. These findings provide a rational explanation for the intermediate-late temporal pattern of expression of the p30tof, p13, and p12/8 mRNAs described in previous studies. All the Rex-dependent mRNAs contained a 75-nucleotide intronic region that increased the nuclear retention and degradation of a reporter mRNA in the absence of other viral sequences. Selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) analysis revealed that this sequence formed a stable hairpin structure. Cell cycle synchronization experiments indicated that mitosis partially bypasses the requirement for Rex to export Rex-dependent HTLV-1 transcripts. These findings indicate a link between the cycling properties of the host cell and the temporal pattern of viral expression/latency that might influence the ability of the virus to spread and evade the immune system. IMPORTANCE: HTLV-1 is a complex retrovirus that causes two distinct pathologies termed adult T-cell leukemia/lymphoma and tropical spastic paraparesis/HTLV-1-associated myelopathy in about 5% of infected individuals. Expression of the virus depends on the concerted action of Tax, which drives transcription of the viral genome, and Rex, which favors expression of incompletely spliced mRNAs and determines a 2-phase temporal pattern of virus expression. The findings reported in this study revealed a novel cis-acting regulatory element and indicated that mitosis partially bypasses the requirement for Rex to export Rex-dependent HTLV-1 transcripts. Our results add a layer of complexity to the mechanisms controlling the expression of alternatively spliced HTLV-1 mRNAs and suggest a link between the cycling properties of the host cell and the temporal pattern of viral expression/latency that might influence the ability of the virus to spread and evade the immune system.
[Mh] Termos MeSH primário: Regulação Viral da Expressão Gênica
Interações Hospedeiro-Patógeno
Vírus 1 Linfotrópico T Humano/genética
Mitose
Processamento de RNA
RNA Mensageiro/metabolismo
RNA Viral/metabolismo
[Mh] Termos MeSH secundário: Expressão Gênica
Perfilação da Expressão Gênica
Técnicas de Inativação de Genes
Produtos do Gene rex/deficiência
Produtos do Gene rex/genética
Células HeLa
Seres Humanos
RNA Mensageiro/genética
RNA Viral/genética
Sequências Reguladoras de Ácido Ribonucleico
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., INTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Gene Products, rex); 0 (RNA, Messenger); 0 (RNA, Viral); 0 (Regulatory Sequences, Ribonucleic Acid); 0 (rex Protein, Human T-lymphotropic virus 1)
[Em] Mês de entrada:1605
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151120
[St] Status:MEDLINE
[do] DOI:10.1128/JVI.02298-15


  3 / 210 MEDLINE  
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[PMID]:26133546
[Au] Autor:Rende F; Cavallari I; Andresen V; Valeri VW; D'Agostino DM; Franchini G; Ciminale V
[Ad] Endereço:Department of Surgery, Oncology and Gastroenterology, University of Padova, Padua, Italy. francesca.rende@unipd.it.
[Ti] Título:Identification of novel monocistronic HTLV-1 mRNAs encoding functional Rex isoforms.
[So] Source:Retrovirology;12:58, 2015 Jul 02.
[Is] ISSN:1742-4690
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Human T cell leukemia virus type 1 (HTLV-1) gene expression is controlled by the key regulatory proteins Tax and Rex. The concerted action of these proteins results in a two-phase kinetics of viral expression that depends on a time delay between their action. However, it is difficult to explain this delay, as Tax and Rex are produced from the same mRNA. In the present study we investigated whether HTLV-1 may produce novel mRNA species capable of expressing Rex and Tax independently. FINDINGS: Results revealed the expression of three alternatively spliced transcripts coding for novel Rex isoforms in infected cell lines and in primary samples from infected patients. One mRNA coded for a Tax isoform and a Rex isoform, and two mRNAs coded for Rex isoforms but not Tax. Functional assays showed that these Rex isoforms exhibit activity comparable to canonic Rex. An analysis of the temporal expression of these transcripts upon ex vivo culture of cells from infected patients and cell lines transfected with a molecular clone of HTLV-1 revealed early expression of the dicistronic tax/rex mRNAs followed by the monocistronic mRNAs coding for Rex isoforms. CONCLUSION: The production of monocistronic HTLV-1 mRNAs encoding Rex isoforms with comparable activity to canonical Rex, but with distinct timing, would support a prolonged duration of Rex function with gradual loss of Tax, and is consistent with the two-phase expression kinetics. A thorough understanding of these regulatory circuits will shed light on the basis of viral latency and provide groundwork to develop strategies for eradicating persistent infections.
[Mh] Termos MeSH primário: Regulação Viral da Expressão Gênica
Produtos do Gene rex/biossíntese
Produtos do Gene rex/genética
Vírus 1 Linfotrópico T Humano/genética
Isoformas de Proteínas/biossíntese
Isoformas de Proteínas/genética
RNA Mensageiro/análise
[Mh] Termos MeSH secundário: Perfilação da Expressão Gênica
Seres Humanos
Processamento de RNA
RNA Mensageiro/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Gene Products, rex); 0 (Protein Isoforms); 0 (RNA, Messenger); 0 (rex Protein, Human T-lymphotropic virus 1)
[Em] Mês de entrada:1603
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150703
[St] Status:MEDLINE
[do] DOI:10.1186/s12977-015-0184-2


  4 / 210 MEDLINE  
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[PMID]:25527330
[Au] Autor:Zheng Y; Ko TP; Yang Y; Shao W; Guo RT
[Ad] Endereço:Industrial Enzymes National Engineering Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China.
[Ti] Título:Binding mode of the oxidized α-anomer of NAD+ to RSP, a Rex-family repressor.
[So] Source:Biochem Biophys Res Commun;456(3):733-6, 2015 Jan 16.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The Rex-family repressors sense redox levels by alternative binding to NADH or NAD(+). RSP is the homologue of Rex in Thermoanaerobacter ethanolicus JW200(T) and regulates ethanol fermentation in this obligate anaerobe. The dimeric repressor binds to DNA by an open conformation. The crystal structure of RSP/α-NAD(+) complex shows a different set of ligand interactions mainly due to the unique configuration of the nicotinamide moiety. The positively charged ring is covered by the Tyr102 side chain and interacts with a sulfate ion adjacent to the N-terminus of helix α8. Consequently, the RSP dimer may be locked in a closed conformation that does not bind to DNA. However, α-NAD(+) does not show a higher affinity to RSP than ß-NAD(+). It has to be improved for possible use as an effector in modulating the repressor.
[Mh] Termos MeSH primário: Proteínas de Bactérias/química
Produtos do Gene rex/química
NAD/química
Proteínas Repressoras/química
Thermoanaerobacter/metabolismo
[Mh] Termos MeSH secundário: Cristalografia por Raios X
Isomerismo
Oxirredução
Ligação Proteica
Conformação Proteica
Multimerização Proteica
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Gene Products, rex); 0 (Repressor Proteins); 0U46U6E8UK (NAD)
[Em] Mês de entrada:1503
[Cu] Atualização por classe:150110
[Lr] Data última revisão:
150110
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:141221
[St] Status:MEDLINE


  5 / 210 MEDLINE  
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[PMID]:25180458
[Au] Autor:Matsumura S; Higa K; Igarashi T; Takaichi S; Tonogi M; Shinozaki N; Shimazaki J; Yamane GY
[Ad] Endereço:Department of Oral Medicine, Oral and Maxillofacial Surgery, Tokyo Dental College, Chiba, Japan.
[Ti] Título:Characterization of mesenchymal progenitor cell populations from non-epithelial oral mucosa.
[So] Source:Oral Dis;21(3):361-72, 2015 Apr.
[Is] ISSN:1601-0825
[Cp] País de publicação:Denmark
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: The characteristics of cell populations extracted from oral mucosal non-epithelial tissues and their ability to differentiate were evaluated in vitro as a potential source of cells for mandibular and corneal regeneration. MATERIALS AND METHODS: Oral mucosal non-epithelial cells (OMNECs) were extracted from tissue samples and were studied by flow cytometry and RT-PCR. Cells differentiating into osteoblasts, adipocytes, chondrocytes, neurocytes, or keratocytes were characterized by RT-PCR and cell staining. RESULTS: OMNECs expressed CD44, CD90, CD105, CD166, and STRO-1 antigens, which are markers for mesenchymal stem cells. In addition, Oct3/4, c-Myc, Nanog, KLF4, and Rex, which are expressed by embryonic or pluripotent stem cells, were detected by RT-PCR. Expression of CD49d, CD56, and PDGFRα, proteins closely associated with the neural crest, was observed in OMNECs, as was expression of Twist1, Sox9, Snail1 and Snail2, which are early neural crest and neural markers. Specific differentiation markers were expressed in OMNECs after differentiation into osteoblasts, adipocytes, chondrocytes, or keratocytes. CONCLUSIONS: Populations of OMNECs may contain both mesenchymal stem cells and neural crest origin cells and are a potential cell source for autologous regeneration of mandibular or corneal stroma.
[Mh] Termos MeSH primário: Antígenos CD/metabolismo
Expressão Gênica
Células Mesenquimais Estromais/citologia
Mucosa Bucal/citologia
Fatores de Transcrição/metabolismo
[Mh] Termos MeSH secundário: Adipócitos/metabolismo
Adulto
Antígenos CD/genética
Antígenos de Superfície/genética
Diferenciação Celular
Células Cultivadas
Condrócitos/metabolismo
Produtos do Gene rex/genética
Seres Humanos
Queratinócitos/metabolismo
Masculino
Células Mesenquimais Estromais/fisiologia
Meia-Idade
Proteína Homeobox Nanog/genética
Osteoblastos/metabolismo
Proteínas Proto-Oncogênicas c-myc/genética
Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo
Fatores de Transcrição/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antigens, CD); 0 (Antigens, Surface); 0 (Gene Products, rex); 0 (MYC protein, human); 0 (NANOG protein, human); 0 (Nanog Homeobox Protein); 0 (Proto-Oncogene Proteins c-myc); 0 (STRO-1 antigen, human); 0 (Transcription Factors); EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor alpha)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:D
[Da] Data de entrada para processamento:140903
[St] Status:MEDLINE
[do] DOI:10.1111/odi.12288


  6 / 210 MEDLINE  
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[PMID]:25216269
[Au] Autor:Laouami S; Clair G; Armengaud J; Duport C
[Ad] Endereço:Avignon Université/INRA, SQPOV UMR408, Avignon, France; INRA, SQPOV UMR408, Avignon, France.
[Ti] Título:Proteomic evidences for rex regulation of metabolism in toxin-producing Bacillus cereus ATCC 14579.
[So] Source:PLoS One;9(9):e107354, 2014.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The facultative anaerobe, Bacillus cereus, causes diarrheal diseases in humans. Its ability to deal with oxygen availability is recognized to be critical for pathogenesis. The B. cereus genome comprises a gene encoding a protein with high similarities to the redox regulator, Rex, which is a central regulator of anaerobic metabolism in Bacillus subtilis and other Gram-positive bacteria. Here, we showed that B. cereus rex is monocistronic and down-regulated in the absence of oxygen. The protein encoded by rex is an authentic Rex transcriptional factor since its DNA binding activity depends on the NADH/NAD+ ratio. Rex deletion compromised the ability of B. cereus to cope with external oxidative stress under anaerobiosis while increasing B. cereus resistance against such stress under aerobiosis. The deletion of rex affects anaerobic fermentative and aerobic respiratory metabolism of B. cereus by decreasing and increasing, respectively, the carbon flux through the NADH-recycling lactate pathway. We compared both the cellular proteome and exoproteome of the wild-type and Δrex cells using a high throughput shotgun label-free quantitation approach and identified proteins that are under control of Rex-mediated regulation. Proteomics data have been deposited to the ProteomeXchange with identifier PXD000886. The data suggest that Rex regulates both the cross-talk between metabolic pathways that produce NADH and NADPH and toxinogenesis, especially in oxic conditions.
[Mh] Termos MeSH primário: Bacillus cereus/genética
Produtos do Gene rex/biossíntese
Proteínas de Membrana/biossíntese
Proteômica
[Mh] Termos MeSH secundário: Anaerobiose/genética
Bacillus cereus/metabolismo
DNA Bacteriano/genética
Enterotoxinas/biossíntese
Enterotoxinas/metabolismo
Exotoxinas/biossíntese
Exotoxinas/genética
Regulação Bacteriana da Expressão Gênica
Produtos do Gene rex/genética
Seres Humanos
Proteínas de Membrana/genética
Redes e Vias Metabólicas/genética
Chaperonas Moleculares/biossíntese
Chaperonas Moleculares/genética
NAD/metabolismo
Ligação Proteica/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (DNA, Bacterial); 0 (Enterotoxins); 0 (Exotoxins); 0 (Gene Products, rex); 0 (Membrane Proteins); 0 (Molecular Chaperones); 0U46U6E8UK (NAD)
[Em] Mês de entrada:1512
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140913
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0107354


  7 / 210 MEDLINE  
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[PMID]:24699669
[Au] Autor:Philip S; Zahoor MA; Zhi H; Ho YK; Giam CZ
[Ad] Endereço:Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America.
[Ti] Título:Regulation of human T-lymphotropic virus type I latency and reactivation by HBZ and Rex.
[So] Source:PLoS Pathog;10(4):e1004040, 2014 Apr.
[Is] ISSN:1553-7374
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Human T lymphotropic virus type I (HTLV-I) infection is largely latent in infected persons. How HTLV-1 establishes latency and reactivates is unclear. Here we show that most HTLV-1-infected HeLa cells become senescent. By contrast, when NF-κB activity is blocked, senescence is averted, and infected cells continue to divide and chronically produce viral proteins. A small population of infected NF-κB-normal HeLa cells expresses low but detectable levels of Tax and Rex, albeit not Gag or Env. In these "latently" infected cells, HTLV-1 LTR trans-activation by Tax persists, but NF-κB trans-activation is attenuated due to inhibition by HBZ, the HTLV-1 antisense protein. Furthermore, Gag-Pol mRNA localizes primarily in the nuclei of these cells. Importantly, HBZ was found to inhibit Rex-mediated export of intron-containing mRNAs. Over-expression of Rex or shRNA-mediated silencing of HBZ led to viral reactivation. Importantly, strong NF-κB inhibition also reactivates HTLV-1. Hence, during HTLV-1 infection, when Tax/Rex expression is robust and dominant over HBZ, productive infection ensues with expression of structural proteins and NF-κB hyper-activation, which induces senescence. When Tax/Rex expression is muted and HBZ is dominant, latent infection is established with expression of regulatory (Tax/Rex/HBZ) but not structural proteins. HBZ maintains viral latency by down-regulating Tax-induced NF-κB activation and senescence, and by inhibiting Rex-mediated expression of viral structural proteins.
[Mh] Termos MeSH primário: Fatores de Transcrição de Zíper de Leucina Básica/metabolismo
Regulação Viral da Expressão Gênica/fisiologia
Produtos do Gene rex/metabolismo
Infecções por HTLV-I/metabolismo
Vírus 1 Linfotrópico T Humano/fisiologia
Ativação Transcricional/fisiologia
Proteínas Virais/metabolismo
Latência Viral/fisiologia
[Mh] Termos MeSH secundário: Fatores de Transcrição de Zíper de Leucina Básica/genética
Núcleo Celular/genética
Núcleo Celular/metabolismo
Núcleo Celular/virologia
Produtos do Gene rex/genética
Produtos do Gene tax
Infecções por HTLV-I/genética
Células HeLa
Seres Humanos
RNA Viral/biossíntese
RNA Viral/genética
Proteínas dos Retroviridae
Proteínas Virais/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Basic-Leucine Zipper Transcription Factors); 0 (Gene Products, rex); 0 (Gene Products, tax); 0 (HBZ protein, human T-cell leukemia virus type I); 0 (RNA, Viral); 0 (Retroviridae Proteins); 0 (Viral Proteins); 0 (rex Protein, Human T-lymphotropic virus 1); 0 (tax protein, Human T-lymphotrophic virus 1)
[Em] Mês de entrada:1412
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140405
[St] Status:MEDLINE
[do] DOI:10.1371/journal.ppat.1004040


  8 / 210 MEDLINE  
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[PMID]:23541980
[Au] Autor:Nakano K; Ando T; Yamagishi M; Yokoyama K; Ishida T; Ohsugi T; Tanaka Y; Brighty DW; Watanabe T
[Ad] Endereço:Laboratory of Tumor Cell Biology, Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Minatoku, Tokyo, Japan.
[Ti] Título:Viral interference with host mRNA surveillance, the nonsense-mediated mRNA decay (NMD) pathway, through a new function of HTLV-1 Rex: implications for retroviral replication.
[So] Source:Microbes Infect;15(6-7):491-505, 2013 Jun.
[Is] ISSN:1769-714X
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Nonsense-mediated mRNA decay (NMD) is an essential and conserved cellular mRNA quality control mechanism. RNA signals to express viral genes from overlapping open reading frames potentially initiate NMD, nevertheless it is not clear whether viral RNAs are sensitive to NMD or if viruses have evolved mechanisms to evade NMD. Here we demonstrate that the genomic and full-length mRNAs of Human-T-cell Leukemia Virus type-I (HTLV-1), a retrovirus responsible for Adult T-cell Leukemia (ATL), are sensitive to NMD. They exhibit accelerated turnover in NMD-activated cells, while siRNA-mediated knockdown of NMD-master-regulator, UPF1, promotes enhanced stability of them. These effects on RNA stability were recapitulated by a reporter construct encoding the HTLV-1 translational frameshift signal of gag-pol. In agreement with the RNA stability, viral protein expression from the integrated provirus was inversely correlated with cellular NMD activity. We further demonstrated that the viral RNA-binding protein, Rex, approves the stability of viral RNA by inhibiting NMD. Significantly, Rex establishes a general block to NMD, as both NMD-responsive reporter transcripts and natural host-encoded NMD substrates were stabilized in the presence of Rex. Thus, we suggest that Rex not only stabilizes viral transcripts, but also perturbs cellular mRNA metabolism and host cell homeostasis via inhibition of NMD.
[Mh] Termos MeSH primário: Produtos do Gene rex/metabolismo
Interações Hospedeiro-Patógeno
Vírus 1 Linfotrópico T Humano/fisiologia
Degradação do RNAm Mediada por Códon sem Sentido
Fatores de Virulência/metabolismo
[Mh] Termos MeSH secundário: Seres Humanos
Estabilidade de RNA
RNA Viral/metabolismo
Proteínas Virais/biossíntese
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Gene Products, rex); 0 (RNA, Viral); 0 (Viral Proteins); 0 (Virulence Factors); 0 (rex Protein, Human T-lymphotropic virus 1)
[Em] Mês de entrada:1312
[Cu] Atualização por classe:161020
[Lr] Data última revisão:
161020
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130402
[St] Status:MEDLINE


  9 / 210 MEDLINE  
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[PMID]:23104922
[Au] Autor:Ko NL; Taylor JM; Bellon M; Bai XT; Shevtsov SP; Dundr M; Nicot C
[Ad] Endereço:Department of Pathology and Laboratory Medicine, Center for Viral Oncology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
[Ti] Título:PA28γ is a novel corepressor of HTLV-1 replication and controls viral latency.
[So] Source:Blood;121(5):791-800, 2013 Jan 31.
[Is] ISSN:1528-0020
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:UNLABELLED: The establishment of a latent reservoir by human tumor viruses is a vital step in initiating cellular transformation and represents a major shortcoming to current therapeutic strategies and the ability to eradicate virus-infected cells. Human T-cell leukemia virus type 1 (HTLV-1) establishes a lifelong infection and is linked to adult T-cell leukemia lymphoma (ATLL). Here, we demonstrate that HTLV-1 p30 recruits the cellular proteasome activator PA28γ onto the viral tax/rex mRNA to prevent its nuclear export and suppress virus replication. Interaction of p30 with a PA28γ retaining fully functional proteasome activity is required for p30's ability to repress HTLV-1. Consistently, HTLV-1 molecular clones replicate better and produce more virus particles in PA28γ-deficient cells. These results define a unique and novel role for the cellular factor PA28γ in the control of nuclear RNA trafficking and HTLV-1­induced latency. Importantly, knockdown of PA28γ expression in ATLL cells latently infected with HTLV-1 reactivates expression of viral tax/rex RNA and the Tax protein. Because Tax is the most immunogenic viral antigen and triggers strong CTL responses, our results suggest that PA28γ-targeted therapy may reactivate virus expression from latently infected cells and allow their eradication from the host. KEY POINTS: PA28γ acts as a co-repressor of HTLV-1 p30 to suppress virus replication and is required for the maintenance of viral latency. HTLV-1 has evolved a unique function mediated by its posttranscriptional repressor p30, which is not found in HTLV-2.
[Mh] Termos MeSH primário: Autoantígenos/metabolismo
Vírus 1 Linfotrópico T Humano/fisiologia
Complexo de Endopeptidases do Proteassoma/metabolismo
Latência Viral/fisiologia
Replicação Viral/fisiologia
[Mh] Termos MeSH secundário: Animais
Autoantígenos/genética
Transporte Biológico Ativo/genética
Linhagem Celular
Regulação Viral da Expressão Gênica/fisiologia
Produtos do Gene rex/genética
Produtos do Gene rex/metabolismo
Produtos do Gene tax/genética
Produtos do Gene tax/metabolismo
Seres Humanos
Camundongos
Camundongos Knockout
Complexo de Endopeptidases do Proteassoma/genética
RNA Viral/genética
RNA Viral/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Autoantigens); 0 (Gene Products, rex); 0 (Gene Products, tax); 0 (Ki antigen); 0 (RNA, Viral); 0 (rex Protein, Human T-lymphotropic virus 1); 0 (tax protein, Human T-lymphotrophic virus 1); EC 3.4.25.1 (Proteasome Endopeptidase Complex)
[Em] Mês de entrada:1303
[Cu] Atualização por classe:161019
[Lr] Data última revisão:
161019
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:121030
[St] Status:MEDLINE
[do] DOI:10.1182/blood-2012-03-420414


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[PMID]:22318152
[Au] Autor:Bai XT; Sinha-Datta U; Ko NL; Bellon M; Nicot C
[Ad] Endereço:University of Kansas Medical Center, Department of Pathology and Laboratory Medicine, Center for Viral Oncology, Kansas City, Kansas, USA.
[Ti] Título:Nuclear export and expression of human T-cell leukemia virus type 1 tax/rex mRNA are RxRE/Rex dependent.
[So] Source:J Virol;86(8):4559-65, 2012 Apr.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Human T-cell leukemia virus type 1 (HTLV-1) is a complex retrovirus associated with the lymphoproliferative disease adult T-cell leukemia/lymphoma (ATL) and the neurodegenerative disorder tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM). Replication of HTLV-1 is under the control of two major trans-acting proteins, Tax and Rex. Previous studies suggested that Tax activates transcription from the viral long terminal repeat (LTR) through recruitment of cellular CREB and transcriptional coactivators. Other studies reported that Rex acts posttranscriptionally and allows the cytoplasmic export of unspliced or incompletely spliced viral mRNAs carrying gag/pol and env only. As opposed to HIV's Rev-responsive element (RRE), the Rex-responsive element (RxRE) is present in all viral mRNAs in HTLV-1. However, based on indirect observations, it is believed that nuclear export and expression of the doubly spliced tax/rex RNA are Rex independent. In this study, we demonstrate that Rex does stimulate Tax expression, through nuclear-cytoplasmic export of the tax/rex RNA, even though a Rex-independent basal export mechanism exists. This effect was dependent upon the RxRE element and the RNA-binding activity of Rex. In addition, Rex-mediated export of tax/rex RNA was CRM1 dependent and inhibited by leptomycin B treatment. RNA immunoprecipitation (RNA-IP) experiments confirmed Rex binding to the tax/rex RNA in both transfected cells with HTLV-1 molecular clones and HTLV-1-infected T cells. Since both Rex and p30 interact with the tax/rex RNA and with one another, this may offer a temporal and dynamic regulation of HTLV-1 replication. Our results shed light on HTLV-1 replication and reveal a more complex regulatory network than previously anticipated.
[Mh] Termos MeSH primário: Produtos do Gene rex/genética
Produtos do Gene tax/genética
Vírus 1 Linfotrópico T Humano/genética
Vírus 1 Linfotrópico T Humano/metabolismo
RNA Mensageiro/metabolismo
RNA Viral/metabolismo
[Mh] Termos MeSH secundário: Transporte Ativo do Núcleo Celular
Sequência de Aminoácidos
Sequência de Bases
Linhagem Celular
Nucléolo Celular/metabolismo
Regulação Viral da Expressão Gênica
Ordem dos Genes
Produtos do Gene rex/metabolismo
Produtos do Gene tax/metabolismo
Seres Humanos
Dados de Sequência Molecular
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Gene Products, rex); 0 (Gene Products, tax); 0 (RNA, Messenger); 0 (RNA, Viral)
[Em] Mês de entrada:1206
[Cu] Atualização por classe:161019
[Lr] Data última revisão:
161019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:120210
[St] Status:MEDLINE
[do] DOI:10.1128/JVI.06361-11



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