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Pesquisa : G02.111.780 [Categoria DeCS]
Referências encontradas : 6873 [refinar]
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[PMID]:29422501
[Au] Autor:Collopy LC; Ware TL; Goncalves T; Í Kongsstovu S; Yang Q; Amelina H; Pinder C; Alenazi A; Moiseeva V; Pearson SR; Armstrong CA; Tomita K
[Ad] Endereço:Chromosome Maintenance Group, UCL Cancer Institute, University College London, London, WC1E 6DD, UK.
[Ti] Título:LARP7 family proteins have conserved function in telomerase assembly.
[So] Source:Nat Commun;9(1):557, 2018 02 08.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Understanding the intricacies of telomerase regulation is crucial due to the potential health benefits of modifying its activity. Telomerase is composed of an RNA component and reverse transcriptase. However, additional factors required during biogenesis vary between species. Here we have identified fission yeast Lar7 as a member of the conserved LARP7 family, which includes the Tetrahymena telomerase-binding protein p65 and human LARP7. We show that Lar7 has conserved RNA-recognition motifs, which bind telomerase RNA to protect it from exosomal degradation. In addition, Lar7 is required to stabilise the association of telomerase RNA with the protective complex LSm2-8, and telomerase reverse transcriptase. Lar7 remains a component of the mature telomerase complex and is required for telomerase localisation to the telomere. Collectively, we demonstrate that Lar7 is a crucial player in fission yeast telomerase biogenesis, similarly to p65 in Tetrahymena, and highlight the LARP7 family as a conserved factor in telomere maintenance.
[Mh] Termos MeSH primário: Proteínas Nucleares/genética
Fosfoproteínas/genética
Proteínas de Protozoários/genética
RNA Fúngico/genética
DNA Polimerase Dirigida por RNA/genética
RNA/genética
Ribonucleoproteínas/genética
Schizosaccharomyces/genética
Telomerase/genética
[Mh] Termos MeSH secundário: Motivos de Aminoácidos
Sequência Conservada
Expressão Gênica
Seres Humanos
Isoenzimas/genética
Isoenzimas/metabolismo
Proteínas Nucleares/metabolismo
Fosfoproteínas/metabolismo
Ligação Proteica
Proteínas de Protozoários/metabolismo
RNA/metabolismo
Estabilidade de RNA
RNA Fúngico/metabolismo
DNA Polimerase Dirigida por RNA/metabolismo
Ribonucleoproteínas/metabolismo
Schizosaccharomyces/metabolismo
Telomerase/metabolismo
Telômero/química
Telômero/ultraestrutura
Tetrahymena thermophila/genética
Tetrahymena thermophila/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Isoenzymes); 0 (Larp7 protein, human); 0 (Nuclear Proteins); 0 (Pdd1 protein, Tetrahymena); 0 (Phosphoproteins); 0 (Protozoan Proteins); 0 (RNA, Fungal); 0 (Ribonucleoproteins); 0 (Ter1 telomerase subunit, S pombe); 63231-63-0 (RNA); EC 2.7.7.49 (RNA-Directed DNA Polymerase); EC 2.7.7.49 (Telomerase)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180210
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02296-4


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[PMID]:29188663
[Au] Autor:Lü YH; Ma KJ; Li ZH; Gu J; Bao JY; Yang ZF; Gao J; Zeng Y; Tao L; Chen L
[Ad] Endereço:Shanghai University of Medicine & Health Science, Shanghai 201318, China.
[Ti] Título:[Correlation between RNA Expression Level and Early PMI in Human Brain Tissue].
[So] Source:Fa Yi Xue Za Zhi;32(4):245-249, 2016 Aug.
[Is] ISSN:1004-5619
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:OBJECTIVES: To explore the correlation between the expression levels of several RNA markers in human brain tissue and early postmortem interval (PMI). METHODS: Twelve individuals with known PMI (range from 4.3 to 22.5 h) were selected and total RNA was extracted from brain tissue. Eight commonly used RNA markers were chosen including -actin, GAPDH, RPS29, 18S rRNA, 5S rRNA, U6 snRNA, miRNA-9 and miRNA-125b, and the expression levels were detected in brain tissue by real-time fluorescent quantitative PCR. The internal reference markers with stable expression in early PMI were screened using geNorm software and the relationship between its expression level and some relevant factors such as age, gender and cause of death were analyzed. RNA markers normalized by internal reference were inserted into the mathematic model established by previous research for PMI estimation using R software. Model quality was judged by the error rate calculated with estimated PMI. RESULTS: 5S rRNA, miRNA-9 and miRNA-125b showed quite stable expression and their expression levels had no relation with age, gender and cause of death. The error rate of estimated PMI using -actin was 24.6%, while GAPDH was 41.0%. CONCLUSIONS: 5S rRNA, miRNA-9 and miRNA-125b are suitable as internal reference markers of human brain tissue owing to their stable expression in early PMI. The expression level of -actin correlates well with PMI, which can be used as an additional index for early PMI estimation.
[Mh] Termos MeSH primário: Encéfalo/metabolismo
MicroRNAs/análise
Mudanças Depois da Morte
RNA Nuclear Pequeno/análise
[Mh] Termos MeSH secundário: Actinas/análise
Autopsia
Seres Humanos
Modelos Teóricos
Estabilidade de RNA
RNA Ribossômico 18S/análise
RNA Ribossômico 5S/análise
Reação em Cadeia da Polimerase em Tempo Real
Software
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Actins); 0 (MicroRNAs); 0 (RNA, Ribosomal, 18S); 0 (RNA, Ribosomal, 5S); 0 (RNA, Small Nuclear); 0 (U6 small nuclear RNA)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171201
[St] Status:MEDLINE
[do] DOI:10.3969/j.issn.1004-5619.2016.04.002


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[PMID]:29254923
[Au] Autor:Lu C; Huang YH
[Ad] Endereço:State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, China.
[Ti] Título:Progress in long non-coding RNAs in animals.
[So] Source:Yi Chuan;39(11):1054-1065, 2017 Nov 20.
[Is] ISSN:0253-9772
[Cp] País de publicação:China
[La] Idioma:eng
[Ab] Resumo:Long non-coding RNAs (lncRNAs) are important transcripts that are more than 200 nucleotides in length, and distribute extensively in animal and plant genomes. Accumulated studies demonstrate that lncRNAs play critical roles in biological processes related to embryogenesis, muscle development, lipid deposition and immune responses. They assist protein complexes in translocating to appropriate locations and participate in regulating gene activation and inactivation. Recently, rapid progress of lncRNA research is emerging, largely due to molecular biological technologies and information developed in the human genome project and the Encyclopedia of DNA Elements (ENCODE) project. For example, a dwarf open reading frame (DWORF) encoded by an annotated lncRNA was reported to activate the SERCA pump. Moreover, small regulatory polypeptide of amino acid response (SPAR) encoded by lncRNA LINC00961 was found to regulate muscle regeneration. These new results have revealed a novel model that lncRNA regulates biological processes using its small peptide product. In this review, we summarize the characteristics, databases, biological functions and molecular regulatory models, as well as research interests of lncRNAs in the future.
[Mh] Termos MeSH primário: RNA Longo não Codificante/fisiologia
[Mh] Termos MeSH secundário: Animais
Desenvolvimento Embrionário
Regulação da Expressão Gênica
Metabolismo dos Lipídeos
Desenvolvimento Muscular
Estabilidade de RNA
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (RNA, Long Noncoding)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171220
[St] Status:MEDLINE
[do] DOI:10.16288/j.yczz.17-120


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[PMID]:28455143
[Au] Autor:Li H; Li B; Larose L
[Ad] Endereço:Department of Medicine, McGill University, Montreal, QC H4A 3J1, Canada; The Research Institute of McGill University Health Centre, Montreal, QC H4A 3J1, Canada.
[Ti] Título:IRE1α links Nck1 deficiency to attenuated PTP1B expression in HepG2 cells.
[So] Source:Cell Signal;36:79-90, 2017 Aug.
[Is] ISSN:1873-3913
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:PTP1B, a prototype of the non-receptor subfamily of the protein tyrosine phosphatase superfamily, plays a key role in regulating intracellular signaling from various receptor and non-receptor protein tyrosine kinases. Previously, we reported that silencing Nck1 in human hepatocellular carcinoma HepG2 cells enhances basal and growth factor-induced activation of the PI3K-Akt pathway through attenuating PTP1B expression. However, the underlying mechanism by which Nck1 depletion represses PTP1B expression remains unclear. In this study, we found that silencing Nck1 attenuates PTP1B expression in HepG2 cells through down-regulation of IRE1α. Indeed, we show that silencing Nck1 in HepG2 cells leads to decreased IRE1α expression and signaling. Accordingly, IRE1α depletion using siRNA in HepG2 cells enhances PI3K-dependent basal and growth factor-induced Akt activation, reproducing the effects of silencing Nck1 on activation of this pathway. In addition, depletion of IRE1α also leads to reduced PTP1B expression, which was rescued by ectopic expression of IRE1α in Nck1-depleted cells. Mechanistically, we found that silencing either Nck1 or IRE1α in HepG2 cells decreases PTP1B mRNA levels and stability. However, despite miR-122 levels, a miRNA targeting PTP1B 3' UTR and inducing PTP1B mRNA degradation in HepG2 cells, are increased in both Nck1- and IRE1α-depleted HepG2 cells, a miR-122 antagomir did not rescue PTP1B expression in these cells. Overall, this study highlights an important role for Nck1 in fine-tuning IRE1α expression and signaling that regulate PTP1B expression and subsequent activation of the PI3K-Akt pathway in HepG2 cells.
[Mh] Termos MeSH primário: Proteínas Adaptadoras de Transdução de Sinal/deficiência
Proteínas Adaptadoras de Transdução de Sinal/metabolismo
Endorribonucleases/metabolismo
Proteínas Oncogênicas/deficiência
Proteínas Oncogênicas/metabolismo
Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo
Proteínas Serina-Treonina Quinases/metabolismo
[Mh] Termos MeSH secundário: Proteínas Adaptadoras de Transdução de Sinal/química
Animais
Ativação Enzimática/efeitos dos fármacos
Fibroblastos/efeitos dos fármacos
Fibroblastos/metabolismo
Inativação Gênica/efeitos dos fármacos
Células HeLa
Células Hep G2
Seres Humanos
Camundongos
MicroRNAs/metabolismo
Proteínas Oncogênicas/química
Fosfatidilinositol 3-Quinases/metabolismo
Fosforilação/efeitos dos fármacos
Ligação Proteica/efeitos dos fármacos
Domínios Proteicos
Proteína Tirosina Fosfatase não Receptora Tipo 1/genética
Proteínas Proto-Oncogênicas c-akt/metabolismo
Estabilidade de RNA/efeitos dos fármacos
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Transdução de Sinais/efeitos dos fármacos
Tapsigargina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adaptor Proteins, Signal Transducing); 0 (MIRN122 microRNA, human); 0 (MicroRNAs); 0 (Nck protein); 0 (Oncogene Proteins); 0 (RNA, Messenger); 67526-95-8 (Thapsigargin); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.11.1 (ERN1 protein, human); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); EC 3.1.- (Endoribonucleases); EC 3.1.3.48 (PTPN1 protein, human); EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 1)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE


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[PMID]:28463111
[Au] Autor:Zhang Z; Hu F; Sung MW; Shu C; Castillo-González C; Koiwa H; Tang G; Dickman M; Li P; Zhang X
[Ad] Endereço:Department of Biochemistry and Biophysics, Texas A&M University, College Station, United States.
[Ti] Título:RISC-interacting clearing 3'- 5' exoribonucleases (RICEs) degrade uridylated cleavage fragments to maintain functional RISC in .
[So] Source:Elife;6, 2017 05 02.
[Is] ISSN:2050-084X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:RNA-induced silencing complex (RISC) is composed of miRNAs and AGO proteins. AGOs use miRNAs as guides to slice target mRNAs to produce truncated 5' and 3' RNA fragments. The 5' cleaved RNA fragments are marked with uridylation for degradation. Here, we identified novel cofactors of Arabidopsis AGOs, named RICE1 and RICE2. RICE proteins specifically degraded single-strand (ss) RNAs in vitro; but neither miRNAs nor miRNA*s in vivo. RICE1 exhibited a DnaQ-like exonuclease fold and formed a homohexamer with the active sites located at the interfaces between RICE1 subunits. Notably, ectopic expression of catalytically-inactive RICE1 not only significantly reduced miRNA levels; but also increased 5' cleavage RISC fragments with extended uridine tails. We conclude that RICEs act to degrade uridylated 5' products of AGO cleavage to maintain functional RISC. Our study also suggests a possible link between decay of cleaved target mRNAs and miRNA stability in RISC.
[Mh] Termos MeSH primário: Arabidopsis/enzimologia
Arabidopsis/genética
Exorribonucleases/metabolismo
Inativação Gênica
Estabilidade de RNA
Complexo de Inativação Induzido por RNA/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (RNA-Induced Silencing Complex); EC 3.1.- (Exoribonucleases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


  6 / 6873 MEDLINE  
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[PMID]:29374155
[Au] Autor:Moon BS; Bai J; Cai M; Liu C; Shi J; Lu W
[Ad] Endereço:Department of Stem Cell Biology and Regenerative Medicine, Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
[Ti] Título:Kruppel-like factor 4-dependent Staufen1-mediated mRNA decay regulates cortical neurogenesis.
[So] Source:Nat Commun;9(1):401, 2018 01 26.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Kruppel-like factor 4 (Klf4) is a zinc-finger-containing protein that plays a critical role in diverse cellular physiology. While most of these functions attribute to its role as a transcription factor, it is postulated that Klf4 may play a role other than transcriptional regulation. Here we demonstrate that Klf4 loss in neural progenitor cells (NPCs) leads to increased neurogenesis and reduced self-renewal in mice. In addition, Klf4 interacts with RNA-binding protein Staufen1 (Stau1) and RNA helicase Ddx5/17. They function together as a complex to maintain NPC self-renewal. We report that Klf4 promotes Stau1 recruitment to the 3'-untranslated region of neurogenesis-associated mRNAs, increasing Stau1-mediated mRNA decay (SMD) of these transcripts. Stau1 depletion abrogated SMD of target mRNAs and rescued neurogenesis defects in Klf4-overexpressing NPCs. Furthermore, Ddx5/17 knockdown significantly blocked Klf4-mediated mRNA degradation. Our results highlight a novel molecular mechanism underlying stability of neurogenesis-associated mRNAs controlled by the Klf4/Ddx5/17/Stau1 axis during mammalian corticogenesis.
[Mh] Termos MeSH primário: Córtex Cerebral/metabolismo
RNA Helicases DEAD-box/genética
Fatores de Transcrição Kruppel-Like/genética
Células-Tronco Neurais/metabolismo
Neurogênese/genética
RNA Mensageiro/genética
Proteínas de Ligação a RNA/genética
[Mh] Termos MeSH secundário: Animais
Proliferação Celular
Córtex Cerebral/citologia
Córtex Cerebral/crescimento & desenvolvimento
RNA Helicases DEAD-box/metabolismo
Embrião de Mamíferos
Feminino
Regulação da Expressão Gênica no Desenvolvimento
Células HEK293
Seres Humanos
Fatores de Transcrição Kruppel-Like/antagonistas & inibidores
Fatores de Transcrição Kruppel-Like/metabolismo
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Células-Tronco Neurais/citologia
Gravidez
Estabilidade de RNA
RNA Mensageiro/metabolismo
RNA Interferente Pequeno/genética
RNA Interferente Pequeno/metabolismo
Proteínas de Ligação a RNA/antagonistas & inibidores
Proteínas de Ligação a RNA/metabolismo
Proteínas de Ligação a RNA/toxicidade
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (GKLF protein); 0 (Kruppel-Like Transcription Factors); 0 (RNA, Messenger); 0 (RNA, Small Interfering); 0 (RNA-Binding Proteins); 0 (Stau1 protein, mouse); EC 3.6.1.- (Ddx17 protein, mouse); EC 3.6.1.- (Ddx5 protein, mouse); EC 3.6.4.13 (DEAD-box RNA Helicases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180128
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02720-9


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[PMID]:28459443
[Au] Autor:Tavernier SJ; Osorio F; Vandersarren L; Vetters J; Vanlangenakker N; Van Isterdael G; Vergote K; De Rycke R; Parthoens E; van de Laar L; Iwawaki T; Del Valle JR; Hu CA; Lambrecht BN; Janssens S
[Ad] Endereço:Laboratory of Immunoregulation and Mucosal Immunology, VIB Center for Inflammation Research, 9052 Ghent, Belgium.
[Ti] Título:Regulated IRE1-dependent mRNA decay sets the threshold for dendritic cell survival.
[So] Source:Nat Cell Biol;19(6):698-710, 2017 Jun.
[Is] ISSN:1476-4679
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The IRE1-XBP1 signalling pathway is part of a cellular programme that protects against endoplasmic reticulum (ER) stress, but also controls development and survival of immune cells. Loss of XBP1 in splenic type 1 conventional dendritic cells (cDC1s) results in functional alterations without affecting cell survival. However, in mucosal cDC1s, loss of XBP1 impaired survival in a tissue-specific manner-while lung cDC1s die, intestinal cDC1s survive. This was not caused by differential activation of ER stress cell-death regulators CHOP or JNK. Rather, survival of intestinal cDC1s was associated with their ability to shut down protein synthesis through a protective integrated stress response and their marked increase in regulated IRE1-dependent messenger RNA decay. Furthermore, loss of IRE1 endonuclease on top of XBP1 led to cDC1 loss in the intestine. Thus, mucosal DCs differentially mount ATF4- and IRE1-dependent adaptive mechanisms to survive in the face of ER stress.
[Mh] Termos MeSH primário: Células Dendríticas/enzimologia
Mucosa Intestinal/enzimologia
Proteínas de Membrana/metabolismo
Proteínas Serina-Treonina Quinases/metabolismo
Estabilidade de RNA
RNA Mensageiro/metabolismo
Mucosa Respiratória/enzimologia
[Mh] Termos MeSH secundário: Fator 4 Ativador da Transcrição/genética
Fator 4 Ativador da Transcrição/metabolismo
Animais
Apoptose
Sobrevivência Celular
Células Dendríticas/patologia
Estresse do Retículo Endoplasmático
Genótipo
Mucosa Intestinal/patologia
Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo
Proteínas de Membrana/genética
Camundongos Transgênicos
Fenótipo
Biossíntese de Proteínas
Proteínas Serina-Treonina Quinases/genética
RNA Mensageiro/genética
Mucosa Respiratória/patologia
Transdução de Sinais
Fatores de Tempo
Fator de Transcrição CHOP/genética
Fator de Transcrição CHOP/metabolismo
Resposta a Proteínas não Dobradas
Proteína 1 de Ligação a X-Box/genética
Proteína 1 de Ligação a X-Box/metabolismo
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Atf4 protein, mouse); 0 (Ddit3 protein, mouse); 0 (Membrane Proteins); 0 (RNA, Messenger); 0 (X-Box Binding Protein 1); 0 (Xbp1 protein, mouse); 145891-90-3 (Activating Transcription Factor 4); 147336-12-7 (Transcription Factor CHOP); EC 2.7.1.- (Ern2 protein, mouse); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE
[do] DOI:10.1038/ncb3518


  8 / 6873 MEDLINE  
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[PMID]:29261646
[Au] Autor:Hamm DC; Larson ED; Nevil M; Marshall KE; Bondra ER; Harrison MM
[Ad] Endereço:Department of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America.
[Ti] Título:A conserved maternal-specific repressive domain in Zelda revealed by Cas9-mediated mutagenesis in Drosophila melanogaster.
[So] Source:PLoS Genet;13(12):e1007120, 2017 12.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In nearly all metazoans, the earliest stages of development are controlled by maternally deposited mRNAs and proteins. The zygotic genome becomes transcriptionally active hours after fertilization. Transcriptional activation during this maternal-to-zygotic transition (MZT) is tightly coordinated with the degradation of maternally provided mRNAs. In Drosophila melanogaster, the transcription factor Zelda plays an essential role in widespread activation of the zygotic genome. While Zelda expression is required both maternally and zygotically, the mechanisms by which it functions to remodel the embryonic genome and prepare the embryo for development remain unclear. Using Cas9-mediated genome editing to generate targeted mutations in the endogenous zelda locus, we determined the functional relevance of protein domains conserved amongst Zelda orthologs. We showed that neither a conserved N-terminal zinc finger nor an acidic patch were required for activity. Similarly, a previously identified splice isoform of zelda is dispensable for viability. By contrast, we identified a highly conserved zinc-finger domain that is essential for the maternal, but not zygotic functions of Zelda. Animals homozygous for mutations in this domain survived to adulthood, but embryos inheriting these loss-of-function alleles from their mothers died late in embryogenesis. These mutations did not interfere with the capacity of Zelda to activate transcription in cell culture. Unexpectedly, these mutations generated a hyperactive form of the protein and enhanced Zelda-dependent gene expression. These data have defined a protein domain critical for controlling Zelda activity during the MZT, but dispensable for its roles later in development, for the first time separating the maternal and zygotic requirements for Zelda. This demonstrates that highly regulated levels of Zelda activity are required for establishing the developmental program during the MZT. We propose that tightly regulated gene expression is essential to navigate the MZT and that failure to precisely execute this developmental program leads to embryonic lethality.
[Mh] Termos MeSH primário: Proteínas de Drosophila/genética
Proteínas de Drosophila/metabolismo
Herança Materna/genética
Fatores de Transcrição/genética
Fatores de Transcrição/metabolismo
[Mh] Termos MeSH secundário: Animais
Sistemas CRISPR-Cas
Sequência Conservada
Drosophila melanogaster
Edição de Genes
Regulação da Expressão Gênica no Desenvolvimento
Mutação
Regiões Promotoras Genéticas
Domínios Proteicos
Estabilidade de RNA/genética
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Dedos de Zinco/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Drosophila Proteins); 0 (RNA, Messenger); 0 (Transcription Factors); 0 (Zelda protein, Drosophila)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171221
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1007120


  9 / 6873 MEDLINE  
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[PMID]:29352242
[Au] Autor:Cottrell KA; Chaudhari HG; Cohen BA; Djuranovic S
[Ad] Endereço:Department of Cell Biology and Physiology, School of Medicine, Washington University, St. Louis, MO, 63110, USA.
[Ti] Título:PTRE-seq reveals mechanism and interactions of RNA binding proteins and miRNAs.
[So] Source:Nat Commun;9(1):301, 2018 01 19.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:RNA binding proteins (RBP) and microRNAs (miRNAs) often bind sequences in 3' untranslated regions (UTRs) of mRNAs, and regulate stability and translation efficiency. With the identification of numerous RBPs and miRNAs, there is an urgent need for new technologies to dissect the function of the cis-acting elements of RBPs and miRNAs. We describe post-transcriptional regulatory element sequencing (PTRE-seq), a massively parallel method for assaying the target sequences of miRNAs and RBPs. We use PTRE-seq to dissect sequence preferences and interactions between miRNAs and RBPs. The binding sites for these effector molecules influenced different aspects of the RNA lifecycle: RNA stability, translation efficiency, and translation initiation. In some cases, post-transcriptional control is modular, with different factors acting independently of each other, while in other cases factors show specific epistatic interactions. The throughput, flexibility, and reproducibility of PTRE-seq make it a valuable tool to study post-transcriptional regulation by 3'UTR elements.
[Mh] Termos MeSH primário: MicroRNAs/genética
Biossíntese de Proteínas
Processamento Pós-Transcricional do RNA
Proteínas de Ligação a RNA/genética
Elementos Reguladores de Transcrição
Fatores de Transcrição/genética
[Mh] Termos MeSH secundário: Regiões 3' não Traduzidas
Sequência de Bases
Sítios de Ligação
Linhagem Celular
Biblioteca Gênica
Células HEK293
Células HeLa
Seres Humanos
MicroRNAs/metabolismo
Ligação Proteica
Estabilidade de RNA
Proteínas de Ligação a RNA/metabolismo
Análise de Sequência de RNA
Termodinâmica
Fatores de Transcrição/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (3' Untranslated Regions); 0 (MicroRNAs); 0 (RNA-Binding Proteins); 0 (Transcription Factors); 0 (mirnlet7 microRNA, human); 0 (pumilio protein, human)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180121
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02745-0


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[PMID]:29352114
[Au] Autor:Rehage N; Davydova E; Conrad C; Behrens G; Maiser A; Stehklein JE; Brenner S; Klein J; Jeridi A; Hoffmann A; Lee E; Dianzani U; Willemsen R; Feederle R; Reiche K; Hackermüller J; Leonhardt H; Sharma S; Niessing D; Heissmeyer V
[Ad] Endereço:Institute for Immunology at the Biomedical Center, Ludwig-Maximilians-Universität München, Grosshaderner Strasse 9, 82152, Planegg-Martinsried, Germany.
[Ti] Título:Binding of NUFIP2 to Roquin promotes recognition and regulation of ICOS mRNA.
[So] Source:Nat Commun;9(1):299, 2018 01 19.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The ubiquitously expressed RNA-binding proteins Roquin-1 and Roquin-2 are essential for appropriate immune cell function and postnatal survival of mice. Roquin proteins repress target mRNAs by recognizing secondary structures in their 3'-UTRs and by inducing mRNA decay. However, it is unknown if other cellular proteins contribute to target control. To identify cofactors of Roquin, we used RNA interference to screen ~1500 genes involved in RNA-binding or mRNA degradation, and identified NUFIP2 as a cofactor of Roquin-induced mRNA decay. NUFIP2 binds directly and with high affinity to Roquin, which stabilizes NUFIP2 in cells. Post-transcriptional repression of human ICOS by endogenous Roquin proteins requires two neighboring non-canonical stem-loops in the ICOS 3'-UTR. This unconventional cis-element as well as another tandem loop known to confer Roquin-mediated regulation of the Ox40 3'-UTR, are bound cooperatively by Roquin and NUFIP2. NUFIP2 therefore emerges as a cofactor that contributes to mRNA target recognition by Roquin.
[Mh] Termos MeSH primário: Linfócitos T CD4-Positivos/imunologia
Proteína Coestimuladora de Linfócitos T Induzíveis/genética
Proteínas Nucleares/genética
Proteínas de Ligação a RNA/genética
Receptores OX40/genética
Proteínas Repressoras/genética
Ubiquitina-Proteína Ligases/genética
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Sítios de Ligação
Linfócitos T CD4-Positivos/citologia
Regulação da Expressão Gênica
Células HEK293
Células HeLa
Seres Humanos
Proteína Coestimuladora de Linfócitos T Induzíveis/antagonistas & inibidores
Proteína Coestimuladora de Linfócitos T Induzíveis/imunologia
Sequências Repetidas Invertidas
Camundongos
Camundongos Endogâmicos C57BL
Proteínas Nucleares/antagonistas & inibidores
Proteínas Nucleares/imunologia
Conformação de Ácido Nucleico
Cultura Primária de Células
Ligação Proteica
Estabilidade de RNA
RNA Interferente Pequeno/genética
RNA Interferente Pequeno/metabolismo
Proteínas de Ligação a RNA/antagonistas & inibidores
Proteínas de Ligação a RNA/imunologia
Receptores OX40/antagonistas & inibidores
Receptores OX40/imunologia
Proteínas Recombinantes/genética
Proteínas Recombinantes/imunologia
Proteínas Repressoras/imunologia
Alinhamento de Sequência
Homologia de Sequência de Aminoácidos
Ubiquitina-Proteína Ligases/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (ICOS protein, human); 0 (Inducible T-Cell Co-Stimulator Protein); 0 (NUFIP2 protein, human); 0 (Nuclear Proteins); 0 (RC3H1 protein, human); 0 (RNA, Small Interfering); 0 (RNA-Binding Proteins); 0 (Receptors, OX40); 0 (Recombinant Proteins); 0 (Repressor Proteins); 0 (TNFRSF4 protein, human); 0 (roquin-2 protein, human); EC 2.3.2.27 (Ubiquitin-Protein Ligases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180121
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02582-1



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