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Pesquisa : D13.444.735.628.818.800 [Categoria DeCS]
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  1 / 835 MEDLINE  
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[PMID]:29385175
[Au] Autor:Firdaus-Raih M; Hashim NHF; Bharudin I; Abu Bakar MF; Huang KK; Alias H; Lee BKB; Mat Isa MN; Mat-Sharani S; Sulaiman S; Tay LJ; Zolkefli R; Muhammad Noor Y; Law DSN; Abdul Rahman SH; Md-Illias R; Abu Bakar FD; Najimudin N; Abdul Murad AM; Mahadi NM
[Ad] Endereço:School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi, Selangor, Malaysia.
[Ti] Título:The Glaciozyma antarctica genome reveals an array of systems that provide sustained responses towards temperature variations in a persistently cold habitat.
[So] Source:PLoS One;13(1):e0189947, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Extremely low temperatures present various challenges to life that include ice formation and effects on metabolic capacity. Psyhcrophilic microorganisms typically have an array of mechanisms to enable survival in cold temperatures. In this study, we sequenced and analysed the genome of a psychrophilic yeast isolated in the Antarctic region, Glaciozyma antarctica. The genome annotation identified 7857 protein coding sequences. From the genome sequence analysis we were able to identify genes that encoded for proteins known to be associated with cold survival, in addition to annotating genes that are unique to G. antarctica. For genes that are known to be involved in cold adaptation such as anti-freeze proteins (AFPs), our gene expression analysis revealed that they were differentially transcribed over time and in response to different temperatures. This indicated the presence of an array of adaptation systems that can respond to a changing but persistent cold environment. We were also able to validate the activity of all the AFPs annotated where the recombinant AFPs demonstrated anti-freeze capacity. This work is an important foundation for further collective exploration into psychrophilic microbiology where among other potential, the genes unique to this species may represent a pool of novel mechanisms for cold survival.
[Mh] Termos MeSH primário: Adaptação Fisiológica/genética
Basidiomycota/fisiologia
Temperatura Baixa
Ecossistema
Genoma Fúngico
[Mh] Termos MeSH secundário: Regiões Antárticas
Proteínas Anticongelantes/genética
Basidiomycota/genética
Íntrons
RNA Nucleolar Pequeno/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antifreeze Proteins); 0 (RNA, Small Nucleolar)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180201
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189947


  2 / 835 MEDLINE  
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[PMID]:28448962
[Au] Autor:Muñoz-Culla M; Irizar H; Gorostidi A; Alberro A; Osorio-Querejeta I; Ruiz-Martínez J; Olascoaga J; López de Munain A; Otaegui D
[Ad] Endereço:Multiple Sclerosis Group, Biodonostia Health Research institute, San Sebastian, Spain.
[Ti] Título:Progressive changes in non-coding RNA profile in leucocytes with age.
[So] Source:Aging (Albany NY);9(4):1202-1218, 2017 Apr.
[Is] ISSN:1945-4589
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:It has been observed that immune cell deterioration occurs in the elderly, as well as a chronic low-grade inflammation called inflammaging. These cellular changes must be driven by numerous changes in gene expression and in fact, both protein-coding and non-coding RNA expression alterations have been observed in peripheral blood mononuclear cells from elder people. In the present work we have studied the expression of small non-coding RNA (microRNA and small nucleolar RNA -snoRNA-) from healthy individuals from 24 to 79 years old. We have observed that the expression of 69 non-coding RNAs (56 microRNAs and 13 snoRNAs) changes progressively with chronological age. According to our results, the age range from 47 to 54 is critical given that it is the period when the expression trend (increasing or decreasing) of age-related small non-coding RNAs is more pronounced. Furthermore, age-related miRNAs regulate genes that are involved in immune, cell cycle and cancer-related processes, which had already been associated to human aging. Therefore, human aging could be studied as a result of progressive molecular changes, and different age ranges should be analysed to cover the whole aging process.
[Mh] Termos MeSH primário: Envelhecimento/metabolismo
Leucócitos/metabolismo
RNA Longo não Codificante/biossíntese
RNA Longo não Codificante/genética
Proteínas de Peixe-Zebra/biossíntese
Proteínas de Peixe-Zebra/genética
[Mh] Termos MeSH secundário: Adulto
Idoso
Simulação por Computador
Feminino
Regulação da Expressão Gênica no Desenvolvimento/genética
Seres Humanos
Masculino
Meia-Idade
RNA Mensageiro/biossíntese
RNA Mensageiro/genética
RNA Nucleolar Pequeno/biossíntese
RNA Nucleolar Pequeno/genética
Transcriptoma
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Long Noncoding); 0 (RNA, Messenger); 0 (RNA, Small Nucleolar); 0 (Zebrafish Proteins)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170428
[St] Status:MEDLINE
[do] DOI:10.18632/aging.101220


  3 / 835 MEDLINE  
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[PMID]:28461681
[Au] Autor:Wise JA; Nielsen O
[Ad] Endereço:Center for RNA Molecular Biology and Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106-4906 jaw17@case.edu.
[Ti] Título:Analysis of RNA Metabolism in Fission Yeast.
[So] Source:Cold Spring Harb Protoc;2017(5):pdb.top079798, 2017 May 01.
[Is] ISSN:1559-6095
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Here we focus on the biogenesis and function of messenger RNA (mRNA) in fission yeast cells. Following a general introduction that also briefly touches on other classes of RNA, we provide an overview of methods used to analyze mRNAs throughout their life cycles.
[Mh] Termos MeSH primário: RNA Fúngico/metabolismo
Schizosaccharomyces/genética
[Mh] Termos MeSH secundário: Biossíntese de Proteínas
Processamento de RNA
RNA Mensageiro/metabolismo
RNA Ribossômico/metabolismo
RNA Interferente Pequeno/metabolismo
RNA Nucleolar Pequeno/metabolismo
RNA de Transferência/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Fungal); 0 (RNA, Messenger); 0 (RNA, Ribosomal); 0 (RNA, Small Interfering); 0 (RNA, Small Nucleolar); 9014-25-9 (RNA, Transfer)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180129
[Lr] Data última revisão:
180129
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1101/pdb.top079798


  4 / 835 MEDLINE  
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[PMID]:28456523
[Au] Autor:Chikne V; Gupta SK; Doniger T; K SR; Cohen-Chalamish S; Waldman Ben-Asher H; Kolet L; Yahia NH; Unger R; Ullu E; Kolev NG; Tschudi C; Michaeli S
[Ad] Endereço:The Mina and Everard Goodman Faculty of Life Sciences and Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan 5290002, Israel.
[Ti] Título:The Canonical Poly (A) Polymerase PAP1 Polyadenylates Non-Coding RNAs and Is Essential for snoRNA Biogenesis in Trypanosoma brucei.
[So] Source:J Mol Biol;429(21):3301-3318, 2017 Oct 27.
[Is] ISSN:1089-8638
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The parasite Trypanosoma brucei is the causative agent of African sleeping sickness and is known for its unique RNA processing mechanisms that are common to all the kinetoplastidea including Leishmania and Trypanosoma cruzi. Trypanosomes possess two canonical RNA poly (A) polymerases (PAPs) termed PAP1 and PAP2. PAP1 is encoded by one of the only two genes harboring cis-spliced introns in this organism, and its function is currently unknown. In trypanosomes, all mRNAs, and non-coding RNAs such as small nucleolar RNAs (snoRNAs) and long non-coding RNAs (lncRNAs), undergo trans-splicing and polyadenylation. Here, we show that the function of PAP1, which is located in the nucleus, is to polyadenylate non-coding RNAs, which undergo trans-splicing and polyadenylation. Major substrates of PAP1 are the snoRNAs and lncRNAs. Under the silencing of either PAP1 or PAP2, the level of snoRNAs is reduced. The dual polyadenylation of snoRNA intermediates is carried out by both PAP2 and PAP1 and requires the factors essential for the polyadenylation of mRNAs. The dual polyadenylation of the precursor snoRNAs by PAPs may function to recruit the machinery essential for snoRNA processing.
[Mh] Termos MeSH primário: Poli A/genética
Poliadenilação/genética
Polinucleotídeo Adenililtransferase/genética
RNA Mensageiro/genética
RNA Nucleolar Pequeno/biossíntese
RNA não Traduzido/genética
Trypanosoma brucei brucei/enzimologia
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Proteínas Associadas a Pancreatite
Processamento de RNA
Alinhamento de Sequência
Trypanosoma brucei brucei/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Pancreatitis-Associated Proteins); 0 (REG3A protein, human); 0 (RNA, Messenger); 0 (RNA, Small Nucleolar); 0 (RNA, Untranslated); 24937-83-5 (Poly A); EC 2.7.7.19 (Polynucleotide Adenylyltransferase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:180116
[Lr] Data última revisão:
180116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170501
[St] Status:MEDLINE


  5 / 835 MEDLINE  
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[PMID]:28945793
[Au] Autor:Chen L; Yang W; Guo Y; Chen W; Zheng P; Zeng J; Tong W
[Ad] Endereço:Department of Neurosurgery, The People's Hospital of Pudong New Area, Shanghai, PR China.
[Ti] Título:Exosomal lncRNA GAS5 regulates the apoptosis of macrophages and vascular endothelial cells in atherosclerosis.
[So] Source:PLoS One;12(9):e0185406, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Atherosclerosis is universally recognized as a chronic lipid-induced inflammation of the vessel wall. Oxidized low density lipoprotein (oxLDL) drives the onset of atherogenesis involving macrophages and endothelial cells (ECs). Our earlier work showed that expression of long noncoding RNA-growth arrest-specific 5 (lncRNA GAS5) was significantly increased in the plaque of atherosclerosis collected from patients and animal models. In this study, we found that knockdown of lncRNA GAS5 reduced the apoptosis of THP-1 cells treated with oxLDL. On the contrary, overexpression of lncRNA GAS5 significantly elevated the apoptosis of THP-1 cells after oxLDL stimulation. The expressions of apoptotic factors including Caspases were changed with lncRNA GAS5 levels. Moreover, lncRNA GAS5 was found in THP-1 derived-exosomes after oxLDL stimulation. Exosomes derived from lncRNA GAS5-overexpressing THP-1 cells enhanced the apoptosis of vascular endothelial cells after taking up these exosomes. However, exosomes shed by lncRNA GAS5 knocked-down THP-1 cells inhibited the apoptosis of endothelial cells. These findings reveal the function of lncRNA GAS5 in atherogenesis which regulates the apoptosis of macrophages and endothelial cells via exosomes and suggest that suppressing the lncRNA GAS5 might be an effective way for the therapy of atherosclerosis.
[Mh] Termos MeSH primário: Apoptose/genética
Aterosclerose/genética
RNA Longo não Codificante/genética
[Mh] Termos MeSH secundário: Animais
Apoptose/efeitos dos fármacos
Aterosclerose/metabolismo
Aterosclerose/patologia
Linhagem Celular
Células Endoteliais/metabolismo
Células Endoteliais/patologia
Exossomos/genética
Técnicas de Silenciamento de Genes
Células Endoteliais da Veia Umbilical Humana
Seres Humanos
Lipoproteínas LDL/farmacologia
Macrófagos/efeitos dos fármacos
Macrófagos/metabolismo
Macrófagos/patologia
RNA Longo não Codificante/antagonistas & inibidores
RNA Nucleolar Pequeno/genética
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (GAS5 long non-coding RNA, human); 0 (Lipoproteins, LDL); 0 (RNA, Long Noncoding); 0 (RNA, Small Nucleolar); 0 (growth arrest specific transcript 5); 0 (oxidized low density lipoprotein)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170926
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0185406


  6 / 835 MEDLINE  
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[PMID]:28911119
[Au] Autor:Huang C; Shi J; Guo Y; Huang W; Huang S; Ming S; Wu X; Zhang R; Ding J; Zhao W; Jia J; Huang X; Xiang AP; Shi Y; Yao C
[Ad] Endereço:Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou 510080, China.
[Ti] Título:A snoRNA modulates mRNA 3' end processing and regulates the expression of a subset of mRNAs.
[So] Source:Nucleic Acids Res;45(15):8647-8660, 2017 Sep 06.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:mRNA 3' end processing is an essential step in gene expression. It is well established that canonical eukaryotic pre-mRNA 3' processing is carried out within a macromolecular machinery consisting of dozens of trans-acting proteins. However, it is unknown whether RNAs play any role in this process. Unexpectedly, we found that a subset of small nucleolar RNAs (snoRNAs) are associated with the mammalian mRNA 3' processing complex. These snoRNAs primarily interact with Fip1, a component of cleavage and polyadenylation specificity factor (CPSF). We have functionally characterized one of these snoRNAs and our results demonstrated that the U/A-rich SNORD50A inhibits mRNA 3' processing by blocking the Fip1-poly(A) site (PAS) interaction. Consistently, SNORD50A depletion altered the Fip1-RNA interaction landscape and changed the alternative polyadenylation (APA) profiles and/or transcript levels of a subset of genes. Taken together, our data revealed a novel function for snoRNAs and provided the first evidence that non-coding RNAs may play an important role in regulating mRNA 3' processing.
[Mh] Termos MeSH primário: Processamento de Terminações 3´ de RNA/genética
RNA Mensageiro/metabolismo
RNA Nucleolar Pequeno/fisiologia
[Mh] Termos MeSH secundário: Fator de Especificidade de Clivagem e Poliadenilação/metabolismo
Regulação da Expressão Gênica
Células HeLa
Seres Humanos
Proteínas Monoméricas de Ligação ao GTP/metabolismo
Poli A/metabolismo
Ligação Proteica
RNA Nucleolar Pequeno/metabolismo
Fatores de Poliadenilação e Clivagem de mRNA/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cleavage And Polyadenylation Specificity Factor); 0 (RNA, Messenger); 0 (RNA, Small Nucleolar); 0 (mRNA Cleavage and Polyadenylation Factors); 24937-83-5 (Poly A); EC 3.6.1.- (RRAGA protein, human); EC 3.6.5.2 (Monomeric GTP-Binding Proteins)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170916
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx651


  7 / 835 MEDLINE  
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[PMID]:28817650
[Au] Autor:Nogueira Jorge NA; Wajnberg G; Ferreira CG; de Sa Carvalho B; Passetti F
[Ad] Endereço:Laboratory of Functional Genomics and Bioinformatics, Oswaldo Cruz Institute, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.
[Ti] Título:snoRNA and piRNA expression levels modified by tobacco use in women with lung adenocarcinoma.
[So] Source:PLoS One;12(8):e0183410, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Lung cancer is one of the most frequent types of cancer worldwide. Most patients are diagnosed at advanced stage and thus have poor prognosis. Smoking is a risk factor for lung cancer, however most smokers do not develop lung cancer while 20% of women with lung adenocarcinoma are non-smokers. Therefore, it is possible that these two groups present differences besides the smoking status, including differences in their gene expression signature. The altered expression patterns of non-coding RNAs in complex diseases make them potential biomarkers for diagnosis and treatment. We analyzed data from differentially and constitutively expressed PIWI-interacting RNAs and small nucleolar RNAs from publicly available small RNA high-throughput sequencing data in search of an expression pattern of non-coding RNA that could differentiate these two groups. Here, we report two sets of differentially expressed small non-coding RNAs identified in normal and tumoral tissues of women with lung adenocarcinoma, that discriminate between smokers and non-smokers. Our findings may offer new insights on metabolic alterations caused by tobacco and may be used for early diagnosis of lung cancer.
[Mh] Termos MeSH primário: Adenocarcinoma/genética
Neoplasias Pulmonares/genética
RNA Interferente Pequeno/genética
RNA Nucleolar Pequeno/genética
Fumar
[Mh] Termos MeSH secundário: Feminino
Perfilação da Expressão Gênica
Seres Humanos
Análise de Componente Principal
Fatores de Risco
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Small Interfering); 0 (RNA, Small Nucleolar)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171013
[Lr] Data última revisão:
171013
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170818
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0183410


  8 / 835 MEDLINE  
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[PMID]:28674185
[Au] Autor:Merran J; Corden JL
[Ad] Endereço:Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
[Ti] Título:Yeast RNA-Binding Protein Nab3 Regulates Genes Involved in Nitrogen Metabolism.
[So] Source:Mol Cell Biol;37(18), 2017 Sep 15.
[Is] ISSN:1098-5549
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Termination of RNA polymerase II (Pol II) transcripts occurs through two alternative pathways. Termination of mRNAs is coupled to cleavage and polyadenylation while noncoding transcripts are terminated through the Nrd1-Nab3-Sen1 (NNS) pathway in a process that is linked to RNA degradation by the nuclear exosome. Some mRNA transcripts are also attenuated through premature termination directed by the NNS complex. In this paper we present the results of nuclear depletion of the NNS component Nab3. As expected, many noncoding RNAs fail to terminate properly. In addition, we observe that nitrogen catabolite-repressed genes are upregulated by Nab3 depletion.
[Mh] Termos MeSH primário: Nitrogênio/metabolismo
Proteínas Nucleares/metabolismo
RNA Polimerase II/genética
RNA Mensageiro/genética
RNA Nucleolar Pequeno/genética
Proteínas de Ligação a RNA/metabolismo
Proteínas de Saccharomyces cerevisiae/metabolismo
Saccharomyces cerevisiae/metabolismo
Terminação da Transcrição Genética/fisiologia
[Mh] Termos MeSH secundário: Repressão Catabólica/genética
Códon sem Sentido/genética
Proteínas de Transporte de Glutamato da Membrana Plasmática/genética
Glutamato-Amônia Ligase/antagonistas & inibidores
Glutamato-Amônia Ligase/metabolismo
IMP Desidrogenase/biossíntese
Saccharomyces cerevisiae/genética
Proteínas de Saccharomyces cerevisiae/biossíntese
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Codon, Nonsense); 0 (Glutamate Plasma Membrane Transport Proteins); 0 (NAB3 protein, S cerevisiae); 0 (Nuclear Proteins); 0 (RNA, Messenger); 0 (RNA, Small Nucleolar); 0 (RNA-Binding Proteins); 0 (Saccharomyces cerevisiae Proteins); EC 1.1.1.205 (IMD2 protein, S cerevisiae); EC 1.1.1.205 (IMP Dehydrogenase); EC 2.7.7.- (RNA Polymerase II); EC 6.3.1.2 (Glutamate-Ammonia Ligase); N762921K75 (Nitrogen)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170705
[St] Status:MEDLINE


  9 / 835 MEDLINE  
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[PMID]:28659642
[Au] Autor:Khalaj M; Park CY
[Ad] Endereço:Department of Pathology, NYU School of Medicine, New York, New York 10016, USA.
[Ti] Título:snoRNAs contribute to myeloid leukaemogenesis.
[So] Source:Nat Cell Biol;19(7):758-760, 2017 Jun 29.
[Is] ISSN:1476-4679
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The mechanism of action of oncogenes in acute myeloid leukaemia is poorly understood. A study now shows that the fusion oncoprotein AML1-ETO regulates leukaemogenesis by increasing the expression of small nucleolar RNAs through post-transcriptional mechanisms, resulting in increased ribosomal RNA methylation, protein translation, and promotion of leukaemic-cell self-renewal and growth.
[Mh] Termos MeSH primário: Subunidade alfa 2 de Fator de Ligação ao Core/genética
RNA Nucleolar Pequeno
[Mh] Termos MeSH secundário: Seres Humanos
Leucemia Mieloide Aguda/genética
Proteínas de Fusão Oncogênicas/genética
RNA Ribossômico
Fatores de Transcrição
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Core Binding Factor Alpha 2 Subunit); 0 (Oncogene Proteins, Fusion); 0 (RNA, Ribosomal); 0 (RNA, Small Nucleolar); 0 (Transcription Factors)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171026
[Lr] Data última revisão:
171026
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170630
[St] Status:MEDLINE
[do] DOI:10.1038/ncb3566


  10 / 835 MEDLINE  
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[PMID]:28650479
[Au] Autor:Zhou F; Liu Y; Rohde C; Pauli C; Gerloff D; Köhn M; Misiak D; Bäumer N; Cui C; Göllner S; Oellerich T; Serve H; Garcia-Cuellar MP; Slany R; Maciejewski JP; Przychodzen B; Seliger B; Klein HU; Bartenhagen C; Berdel WE; Dugas M; Taketo MM; Farouq D; Schwartz S; Regev A; Hébert J; Sauvageau G; Pabst C; Hüttelmaier S; Müller-Tidow C
[Ad] Endereço:Department of Hematology and Oncology, University of Halle, Halle 06120, Germany.
[Ti] Título:AML1-ETO requires enhanced C/D box snoRNA/RNP formation to induce self-renewal and leukaemia.
[So] Source:Nat Cell Biol;19(7):844-855, 2017 Jul.
[Is] ISSN:1476-4679
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Leukaemogenesis requires enhanced self-renewal, which is induced by oncogenes. The underlying molecular mechanisms remain incompletely understood. Here, we identified C/D box snoRNAs and rRNA 2'-O-methylation as critical determinants of leukaemic stem cell activity. Leukaemogenesis by AML1-ETO required expression of the groucho-related amino-terminal enhancer of split (AES). AES functioned by inducing snoRNA/RNP formation via interaction with the RNA helicase DDX21. Similarly, global loss of C/D box snoRNAs with concomitant loss of rRNA 2'-O-methylation resulted in decreased leukaemia self-renewal potential. Genomic deletion of either C/D box snoRNA SNORD14D or SNORD35A suppressed clonogenic potential of leukaemia cells in vitro and delayed leukaemogenesis in vivo. We further showed that AML1-ETO9a, MYC and MLL-AF9 all enhanced snoRNA formation. Expression levels of C/D box snoRNAs in AML patients correlated closely with in vivo frequency of leukaemic stem cells. Collectively, these findings indicate that induction of C/D box snoRNA/RNP function constitutes an important pathway in leukaemogenesis.
[Mh] Termos MeSH primário: Proliferação Celular
Autorrenovação Celular
Transformação Celular Neoplásica/metabolismo
Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo
Leucemia/metabolismo
Proteína de Leucina Linfoide-Mieloide/metabolismo
Proteínas de Fusão Oncogênicas/metabolismo
RNA Nucleolar Pequeno/metabolismo
Ribonucleoproteínas/metabolismo
[Mh] Termos MeSH secundário: Animais
Transformação Celular Neoplásica/genética
Transformação Celular Neoplásica/patologia
Subunidade alfa 2 de Fator de Ligação ao Core/genética
RNA Helicases DEAD-box/genética
RNA Helicases DEAD-box/metabolismo
Regulação Leucêmica da Expressão Gênica
Predisposição Genética para Doença
Células HEK293
Células HL-60
Seres Humanos
Células K562
Leucemia/genética
Leucemia/patologia
Metilação
Camundongos Endogâmicos C57BL
Camundongos Knockout
Proteína de Leucina Linfoide-Mieloide/genética
Proteínas de Fusão Oncogênicas/genética
Fenótipo
Mapas de Interação de Proteínas
Proteínas Proto-Oncogênicas c-myc/genética
Proteínas Proto-Oncogênicas c-myc/metabolismo
RNA Ribossômico/genética
RNA Ribossômico/metabolismo
RNA Nucleolar Pequeno/genética
Proteína 1 Parceira de Translocação de RUNX1
Proteínas Repressoras/genética
Proteínas Repressoras/metabolismo
Ribonucleoproteínas/genética
Transdução de Sinais
Fatores de Tempo
Fatores de Transcrição/genética
Fatores de Transcrição/metabolismo
Células U937
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AES protein, human); 0 (AML1-ETO fusion protein, human); 0 (AML1-ETO fusion protein, mouse); 0 (Aes protein, mouse); 0 (Core Binding Factor Alpha 2 Subunit); 0 (MLL-AF9 fusion protein, human); 0 (MYC protein, human); 0 (Oncogene Proteins, Fusion); 0 (Proto-Oncogene Proteins c-myc); 0 (RNA, Ribosomal); 0 (RNA, Small Nucleolar); 0 (RUNX1 Translocation Partner 1 Protein); 0 (Repressor Proteins); 0 (Ribonucleoproteins); 0 (Transcription Factors); 149025-06-9 (Myeloid-Lymphoid Leukemia Protein); EC 3.6.1.- (DDX21 protein, human); EC 3.6.4.13 (DEAD-box RNA Helicases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170627
[St] Status:MEDLINE
[do] DOI:10.1038/ncb3563



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