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Pesquisa : D08.811.277.352.365.300 [Categoria DeCS]
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[PMID]:29311576
[Au] Autor:Razew M; Warkocki Z; Taube M; Kolondra A; Czarnocki-Cieciura M; Nowak E; Labedzka-Dmoch K; Kawinska A; Piatkowski J; Golik P; Kozak M; Dziembowski A; Nowotny M
[Ad] Endereço:Laboratory of Protein Structure, International Institute of Molecular and Cell Biology, Trojdena 4, 02-109, Warsaw, Poland.
[Ti] Título:Structural analysis of mtEXO mitochondrial RNA degradosome reveals tight coupling of nuclease and helicase components.
[So] Source:Nat Commun;9(1):97, 2018 01 08.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Nuclease and helicase activities play pivotal roles in various aspects of RNA processing and degradation. These two activities are often present in multi-subunit complexes from nucleic acid metabolism. In the mitochondrial exoribonuclease complex (mtEXO) both enzymatic activities are tightly coupled making it an excellent minimal system to study helicase-exoribonuclease coordination. mtEXO is composed of Dss1 3'-to-5' exoribonuclease and Suv3 helicase. It is the master regulator of mitochondrial gene expression in yeast. Here, we present the structure of mtEXO and a description of its mechanism of action. The crystal structure of Dss1 reveals domains that are responsible for interactions with Suv3. Importantly, these interactions are compatible with the conformational changes of Suv3 domains during the helicase cycle. We demonstrate that mtEXO is an intimate complex which forms an RNA-binding channel spanning its entire structure, with Suv3 helicase feeding the 3' end of the RNA toward the active site of Dss1.
[Mh] Termos MeSH primário: Endorribonucleases/metabolismo
Exorribonucleases/metabolismo
Proteínas Mitocondriais/metabolismo
Complexos Multienzimáticos/metabolismo
Polirribonucleotídeo Nucleotidiltransferase/metabolismo
RNA Helicases/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Sequência de Bases
Candida glabrata/enzimologia
Candida glabrata/genética
Candida glabrata/metabolismo
Cristalografia por Raios X
RNA Helicases DEAD-box/química
RNA Helicases DEAD-box/genética
RNA Helicases DEAD-box/metabolismo
Endorribonucleases/química
Endorribonucleases/genética
Exorribonucleases/química
Exorribonucleases/genética
Proteínas Mitocondriais/química
Proteínas Mitocondriais/genética
Complexos Multienzimáticos/química
Complexos Multienzimáticos/genética
Conformação de Ácido Nucleico
Polirribonucleotídeo Nucleotidiltransferase/química
Polirribonucleotídeo Nucleotidiltransferase/genética
Ligação Proteica
Conformação Proteica
RNA/química
RNA/genética
RNA/metabolismo
RNA Helicases/química
RNA Helicases/genética
Saccharomyces cerevisiae/enzimologia
Saccharomyces cerevisiae/genética
Saccharomyces cerevisiae/metabolismo
Proteínas de Saccharomyces cerevisiae/química
Proteínas de Saccharomyces cerevisiae/genética
Proteínas de Saccharomyces cerevisiae/metabolismo
Homologia de Sequência de Aminoácidos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Mitochondrial Proteins); 0 (Multienzyme Complexes); 0 (RNA, mitochondrial); 0 (Saccharomyces cerevisiae Proteins); 0 (degradosome); 63231-63-0 (RNA); EC 2.7.7.8 (Polyribonucleotide Nucleotidyltransferase); EC 3.1.- (Endoribonucleases); EC 3.1.- (Exoribonucleases); EC 3.1.13.1 (DSS1 protein, S cerevisiae); EC 3.6.1.- (SUV3 protein, S cerevisiae); EC 3.6.4.13 (DEAD-box RNA Helicases); EC 3.6.4.13 (RNA Helicases)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180110
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02570-5


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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


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[PMID]:27777260
[Au] Autor:Fasken MB; Losh JS; Leung SW; Brutus S; Avin B; Vaught JC; Potter-Birriel J; Craig T; Conn GL; Mills-Lujan K; Corbett AH; van Hoof A
[Ad] Endereço:Department of Biology, Emory University, Atlanta, Georgia 30322.
[Ti] Título:Insight into the RNA Exosome Complex Through Modeling Pontocerebellar Hypoplasia Type 1b Disease Mutations in Yeast.
[So] Source:Genetics;205(1):221-237, 2017 01.
[Is] ISSN:1943-2631
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Pontocerebellar hypoplasia type 1b (PCH1b) is an autosomal recessive disorder that causes cerebellar hypoplasia and spinal motor neuron degeneration, leading to mortality in early childhood. PCH1b is caused by mutations in the RNA exosome subunit gene, EXOSC3 The RNA exosome is an evolutionarily conserved complex, consisting of nine different core subunits, and one or two 3'-5' exoribonuclease subunits, that mediates several RNA degradation and processing steps. The goal of this study is to assess the functional consequences of the amino acid substitutions that have been identified in EXOSC3 in PCH1b patients. To analyze these EXOSC3 substitutions, we generated the corresponding amino acid substitutions in the Saccharomyces cerevisiae ortholog of EXOSC3, Rrp40 We find that the rrp40 variants corresponding to EXOSC3-G31A and -D132A do not affect yeast function when expressed as the sole copy of the essential Rrp40 protein. In contrast, the rrp40-W195R variant, corresponding to EXOSC3-W238R in PCH1b patients, impacts cell growth and RNA exosome function when expressed as the sole copy of Rrp40 The rrp40-W195R protein is unstable, and does not associate efficiently with the RNA exosome in cells that also express wild-type Rrp40 Consistent with these findings in yeast, the levels of mouse EXOSC3 variants are reduced compared to wild-type EXOSC3 in a neuronal cell line. These data suggest that cells possess a mechanism for optimal assembly of functional RNA exosome complex that can discriminate between wild-type and variant exosome subunits. Budding yeast can therefore serve as a useful tool to understand the molecular defects in the RNA exosome caused by PCH1b-associated amino acid substitutions in EXOSC3, and potentially extending to disease-associated substitutions in other exosome subunits.
[Mh] Termos MeSH primário: Doenças Cerebelares/genética
Complexo Multienzimático de Ribonucleases do Exossomo/genética
Mutação
Saccharomyces cerevisiae/genética
[Mh] Termos MeSH secundário: Doenças Cerebelares/metabolismo
Exorribonucleases/genética
Exorribonucleases/metabolismo
Complexo Multienzimático de Ribonucleases do Exossomo/metabolismo
Estabilidade de RNA
Proteínas de Ligação a RNA/genética
Proteínas de Ligação a RNA/metabolismo
Saccharomyces cerevisiae/metabolismo
Proteínas de Saccharomyces cerevisiae/genética
Proteínas de Saccharomyces cerevisiae/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (RNA-Binding Proteins); 0 (Saccharomyces cerevisiae Proteins); EC 3.1.- (Exoribonucleases); EC 3.1.- (Exosome Multienzyme Ribonuclease Complex); EC 3.1.- (Rrp40 protein, S cerevisiae)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:180101
[Lr] Data última revisão:
180101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161027
[St] Status:MEDLINE
[do] DOI:10.1534/genetics.116.195917


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[PMID]:29033321
[Au] Autor:Wojtas MN; Pandey RR; Mendel M; Homolka D; Sachidanandam R; Pillai RS
[Ad] Endereço:Department of Molecular Biology, University of Geneva, 30 Quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland; European Molecular Biology Laboratory, Grenoble Outstation, 71 Avenue des Martyrs, 38042 Grenoble, France.
[Ti] Título:Regulation of m A Transcripts by the 3'→5' RNA Helicase YTHDC2 Is Essential for a Successful Meiotic Program in the Mammalian Germline.
[So] Source:Mol Cell;68(2):374-387.e12, 2017 Oct 19.
[Is] ISSN:1097-4164
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:N -methyladenosine (m A) is an essential internal RNA modification that is critical for gene expression control in most organisms. Proteins with a YTH domain recognize m A marks and are mediators of molecular functions like RNA splicing, mRNA decay, and translation control. Here we demonstrate that YTH domain-containing 2 (YTHDC2) is an m A reader that is essential for male and female fertility in mice. High-throughput mapping of the m A transcriptome and expression analysis in the Yhtdc2 mutant testes reveal an upregulation of m A-enriched transcripts. Our biochemical studies indicate that YTHDC2 is an RNA-induced ATPase with a 3'→5' RNA helicase activity. Furthermore, YTHDC2 recruits the 5'→3' exoribonuclease XRN1 via Ankyrin repeats that are inserted in between the RecA modules of the RNA helicase domain. Our studies reveal a role for YTHDC2 in modulating the levels of m A-modified germline transcripts to maintain a gene expression program that is conducive for progression through meiosis.
[Mh] Termos MeSH primário: Adenosina/análogos & derivados
Regulação da Expressão Gênica/fisiologia
Meiose/fisiologia
RNA Helicases/metabolismo
RNA Mensageiro/metabolismo
[Mh] Termos MeSH secundário: Adenosina/genética
Adenosina/metabolismo
Animais
Repetição de Anquirina
Proteínas de Ligação a DNA/genética
Proteínas de Ligação a DNA/metabolismo
Exorribonucleases/genética
Exorribonucleases/metabolismo
Masculino
Camundongos
Camundongos Mutantes
Domínios Proteicos
RNA Helicases/genética
RNA Mensageiro/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA-Binding Proteins); 0 (RNA, Messenger); 1867-73-8 (N(6)-methyladenosine); EC 3.1.- (Exoribonucleases); EC 3.1.- (Xrn1 protein, mouse); EC 3.6.4.13 (RNA Helicases); K72T3FS567 (Adenosine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171027
[Lr] Data última revisão:
171027
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171017
[St] Status:MEDLINE


  5 / 1747 MEDLINE  
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[PMID]:28867193
[Au] Autor:Qin X; Qiu F; Zou Z
[Ad] Endereço:Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, 400016 Chongqing, China.
[Ti] Título:TRIM25 is associated with cisplatin resistance in non-small-cell lung carcinoma A549 cell line via downregulation of 14-3-3σ.
[So] Source:Biochem Biophys Res Commun;493(1):568-572, 2017 Nov 04.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Lung cancer, in particular, non-small cell lung cancer (NSCLC), is the leading cause of cancer-related mortality. Cis-Diamminedichloroplatinum (cisplatin, CDDP) as first-line chemotherapy for NSCLC, but resistance occurs frequently. We previously reported that Tripartite motif protein 25 (TRIM25) was highly expressed in cisplatin-resistant human lung adenocarcinoma A549 cells (A549/CDDP) in comparison with its parental A549 cells. Herein, we take a further step to demonstrate the association of TRIM25 and cisplatin resistance and also the underlying mechanisms. Knockdown of TRIM25 by RNA interference in A549/CDDP cells decreased half maximal inhibitory concentration (IC ) values and promoted apoptosis in response to cisplatin, whereas overexpression of TRIM25 had opposite effects. More importantly, we found that concomitant knockdown of 14-3-3σ and TRIM25 absolutely reversed the decreased MDM2, increased p53, increased cleaved-Capsese3 and decreased IC value induced by knockdown of TRIM25 individually, suggesting that TRIM25 mediated cisplatin resistance primarily through downregulation of 14-3-3σ. Our results indicate that TRIM25 is associated with cisplatin resistance and 14-3-3σ-MDM2-p53 signaling pathway is involved in this process, suggesting targeting TRIM25 may be a potential strategy for the reversal of cisplatin resistance.
[Mh] Termos MeSH primário: Proteínas 14-3-3/metabolismo
Biomarcadores Tumorais/metabolismo
Cisplatino/administração & dosagem
Regulação para Baixo/efeitos dos fármacos
Resistência a Medicamentos Antineoplásicos/efeitos dos fármacos
Exorribonucleases/metabolismo
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Fatores de Transcrição/metabolismo
Proteínas com Motivo Tripartido/metabolismo
Ubiquitina-Proteína Ligases/metabolismo
[Mh] Termos MeSH secundário: Células A549
Antineoplásicos/administração & dosagem
Relação Dose-Resposta a Droga
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (14-3-3 Proteins); 0 (Antineoplastic Agents); 0 (Biomarkers, Tumor); 0 (Transcription Factors); 0 (Tripartite Motif Proteins); EC 2.3.2.27 (TRIM25 protein, human); EC 2.3.2.27 (Ubiquitin-Protein Ligases); EC 3.1.- (Exoribonucleases); EC 3.1.- (SFN protein, human); Q20Q21Q62J (Cisplatin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170905
[St] Status:MEDLINE


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[PMID]:28809941
[Au] Autor:Harwig A; Kruize Z; Yang Z; Restle T; Berkhout B
[Ad] Endereço:Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
[Ti] Título:Analysis of AgoshRNA maturation and loading into Ago2.
[So] Source:PLoS One;12(8):e0183269, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The RNA interference (RNAi) pathway was recently expanded by the discovery of multiple alternative pathways for processing of natural microRNA (miRNA) and man-made short hairpin RNA (shRNA) molecules. One non-canonical pathway bypasses Dicer cleavage and requires instead processing by Argonaute2 (Ago2), which also executes the subsequent silencing step. We named these molecules AgoshRNA, which generate only a single active RNA strand and thus avoid off-target effects that can be induced by the passenger strand of a regular shRNA. Previously, we characterized AgoshRNA processing by deep sequencing and demonstrated that-after Ago2 cleavage-AgoshRNAs acquire a short 3' tail of 1-3 A-nucleotides and are subsequently trimmed, likely by the poly(A)-specific ribonuclease (PARN). As a result, the mature single-stranded AgoshRNA may dock more stably into Ago2. Here we set out to analyze the activity of different synthetic AgoshRNA processing intermediates. Ago2 was found to bind preferentially to partially single-stranded AgoshRNA in vitro. In contrast, only the double-stranded AgoshRNA precursor associated with Ago2 in cells, correlating with efficient intracellular processing and reporter knockdown activity. These results suggest the presence of a cellular co-factor involved in AgoshRNA loading into Ago2 in vivo. We also demonstrate specific AgoshRNA loading in Ago2, but not Ago1/3/4, thus further reducing unwanted side effects.
[Mh] Termos MeSH primário: Proteínas Argonauta/genética
[Mh] Termos MeSH secundário: Proteínas Argonauta/metabolismo
Exorribonucleases/genética
Exorribonucleases/metabolismo
Células HEK293
Seres Humanos
Imunoprecipitação
MicroRNAs/genética
Ligação Proteica/genética
Ligação Proteica/fisiologia
Interferência de RNA
Processamento Pós-Transcricional do RNA/genética
Processamento Pós-Transcricional do RNA/fisiologia
RNA Interferente Pequeno/genética
RNA Interferente Pequeno/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Argonaute Proteins); 0 (EIF2C2 protein, human); 0 (MicroRNAs); 0 (RNA, Small Interfering); EC 3.1.- (Exoribonucleases); EC 3.1.13.4 (poly(A)-specific ribonuclease)
[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:170816
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0183269


  7 / 1747 MEDLINE  
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[PMID]:28808133
[Au] Autor:Bowden KE; Wiese NS; Perwez T; Mohanty BK; Kushner SR
[Ad] Endereço:Department of Genetics, University of Georgia, Athens, Georgia, USA.
[Ti] Título:The -Encoded Truncated RNase PH Protein Inhibits RNase P Maturation of Pre-tRNAs with Short Leader Sequences in the Absence of RppH.
[So] Source:J Bacteriol;199(22), 2017 Nov 15.
[Is] ISSN:1098-5530
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RNase PH, encoded by the gene, is a 3'→5' exoribonuclease that in participates primarily in the 3' maturation of pre-tRNAs and the degradation of rRNA in stationary-phase cells. Interestingly, the routinely used laboratory strains of MG1655 and W3110 have naturally acquired the allele, encoding a truncated catalytically inactive RNase PH protein which is widely assumed to be benign. Contrary to this assumption, we show that the -encoded Rph-1 protein inhibits RNase P-mediated 5'-end maturation of primary pre-tRNAs with leaders of <5 nucleotides in the absence of RppH, an RNA pyrophosphohydrolase. In contrast, RppH is not required for 5'-end maturation of endonucleolytically generated pre-tRNAs in the strain and for any tRNAs in Δ mutant or strains. We propose that the Rph-1 protein bound to the 3' end of the substrate creates a steric hindrance that in the presence of a triphosphate at the 5' end reduces the ability of RNase P to bind to the pre-tRNA. In this paper, we demonstrate that the mutation found in commonly used strains leads to the synthesis of a truncated functionally inactive RNase PH protein that interferes with the 5'-end maturation of specific tRNAs with short 5' leaders by RNase P in the absence of RppH, an RNA pyrophosphohydrolase that converts primary 5' triphosphates into 5' monophosphates. The data presented indicate that the presence of the triphosphate interferes with RNase P binding to the pre-tRNA.
[Mh] Termos MeSH primário: Hidrolases Anidrido Ácido/genética
Hidrolases Anidrido Ácido/metabolismo
Proteínas de Escherichia coli/genética
Proteínas de Escherichia coli/metabolismo
Exorribonucleases/genética
RNA de Transferência/metabolismo
Ribonuclease P/metabolismo
[Mh] Termos MeSH secundário: Endorribonucleases/genética
Endorribonucleases/metabolismo
Escherichia coli/genética
Escherichia coli/metabolismo
Exorribonucleases/metabolismo
Mutação
Sinais Direcionadores de Proteínas
Precursores de RNA/química
Precursores de RNA/genética
Precursores de RNA/metabolismo
Processamento Pós-Transcricional do RNA
RNA Bacteriano/genética
RNA Bacteriano/metabolismo
RNA de Transferência/química
RNA de Transferência/genética
Ribonuclease P/genética
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Escherichia coli Proteins); 0 (Protein Sorting Signals); 0 (RNA Precursors); 0 (RNA, Bacterial); 9014-25-9 (RNA, Transfer); EC 2.7.7.56 (ribonuclease PH); EC 3.1.- (Endoribonucleases); EC 3.1.- (Exoribonucleases); EC 3.1.26.5 (Ribonuclease P); EC 3.1.4.- (ribonuclease E); EC 3.6.- (Acid Anhydride Hydrolases); EC 3.6.1.- (RppH protein, E coli)
[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:170816
[St] Status:MEDLINE


  8 / 1747 MEDLINE  
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[PMID]:28760775
[Au] Autor:Shukla S; Parker R
[Ad] Endereço:Department of Chemistry and Biochemistry and Howard Hughes Medical Institute, University of Colorado, Boulder, Colorado, USA.
[Ti] Título:PARN Modulates Y RNA Stability and Its 3'-End Formation.
[So] Source:Mol Cell Biol;37(20), 2017 Oct 15.
[Is] ISSN:1098-5549
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Loss-of-function mutations in 3'-to-5' exoribonucleases have been implicated in hereditary human diseases. For example, PARN mutations cause a severe form of dyskeratosis congenita (DC), wherein PARN deficiency leads to human telomerase RNA instability. Since the DC phenotype in PARN patients is even more severe than that of loss-of-function alleles in telomerase components, we hypothesized that PARN would also be required for the stability of other RNAs. Here, we show that PARN depletion reduces the levels of abundant human Y RNAs, which might contribute to the severe phenotype of DC observed in patients. Depletion of PAPD5 or the cytoplasmic exonuclease DIS3L rescues the effect of PARN depletion on Y RNA levels, suggesting that PARN stabilizes Y RNAs by removing oligoadenylated tails added by PAPD5, which would otherwise recruit DIS3L for Y RNA degradation. Through deep sequencing of 3' ends, we provide evidence that PARN can also deadenylate the U6 and RMRP RNAs without affecting their levels. Moreover, we observed widespread posttranscriptional oligoadenylation, uridylation, and guanylation of U6 and Y RNA 3' ends, suggesting that in mammalian cells, the formation of a 3' end for noncoding RNAs can be a complex process governed by the activities of various 3'-end polymerases and exonucleases.
[Mh] Termos MeSH primário: Exorribonucleases/metabolismo
Estabilidade de RNA
RNA/metabolismo
[Mh] Termos MeSH secundário: Alelos
Disceratose Congênita/metabolismo
Células HeLa
Seres Humanos
Mutação/genética
Fenótipo
Telomerase
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (telomerase RNA); 63231-63-0 (RNA); EC 2.7.7.49 (Telomerase); EC 3.1.- (Exoribonucleases); EC 3.1.13.4 (poly(A)-specific ribonuclease)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170802
[St] Status:MEDLINE


  9 / 1747 MEDLINE  
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[PMID]:28681606
[Au] Autor:Sijbesma E; Skora L; Leysen S; Brunsveld L; Koch U; Nussbaumer P; Jahnke W; Ottmann C
[Ad] Endereço:Department of Biomedical Engineering, Laboratory of Chemical Biology, and Institute for Complex Molecular Systems, Eindhoven University of Technology , P.O. Box 513, 5600 MB Eindhoven, The Netherlands.
[Ti] Título:Identification of Two Secondary Ligand Binding Sites in 14-3-3 Proteins Using Fragment Screening.
[So] Source:Biochemistry;56(30):3972-3982, 2017 Aug 01.
[Is] ISSN:1520-4995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Proteins typically interact with multiple binding partners, and often different parts of their surfaces are employed to establish these protein-protein interactions (PPIs). Members of the class of 14-3-3 adapter proteins bind to several hundred other proteins in the cell. Multiple small molecules for the modulation of 14-3-3 PPIs have been disclosed; however, they all target the conserved phosphopeptide binding channel, so that selectivity is difficult to achieve. Here we report on the discovery of two individual secondary binding sites that have been identified by combining nuclear magnetic resonance-based fragment screening and X-ray crystallography. The two pockets that these fragments occupy are part of at least three physiologically relevant and structurally characterized 14-3-3 PPI interfaces, including those with serotonin N-acetyltransferase and plant transcription factor FT. In addition, the high degree of conservation of the two sites implies their relevance for 14-3-3 PPIs. This first identification of secondary sites on 14-3-3 proteins bound by small molecule ligands might facilitate the development of new chemical tool compounds for more selective PPI modulation.
[Mh] Termos MeSH primário: Proteínas 14-3-3/metabolismo
Biomarcadores Tumorais/metabolismo
Exorribonucleases/metabolismo
Modelos Moleculares
Fatores de Transcrição/metabolismo
[Mh] Termos MeSH secundário: Proteínas 14-3-3/química
Proteínas 14-3-3/genética
Sequência de Aminoácidos
Sítios de Ligação
Biomarcadores Tumorais/química
Biomarcadores Tumorais/genética
Sequência Conservada
Cristalografia por Raios X
Exorribonucleases/química
Exorribonucleases/genética
Deleção de Genes
Seres Humanos
Cinética
Ligantes
Ressonância Magnética Nuclear Biomolecular
Fragmentos de Peptídeos/química
Fragmentos de Peptídeos/genética
Fragmentos de Peptídeos/metabolismo
Biblioteca de Peptídeos
Fosforilação
Conformação Proteica
Domínios e Motivos de Interação entre Proteínas
Mapeamento de Interação de Proteínas
Isoformas de Proteínas/química
Isoformas de Proteínas/genética
Isoformas de Proteínas/metabolismo
Processamento de Proteína Pós-Traducional
Proteínas Recombinantes de Fusão/química
Proteínas Recombinantes de Fusão/metabolismo
Proteínas Recombinantes/química
Proteínas Recombinantes/metabolismo
Fatores de Transcrição/química
Fatores de Transcrição/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (14-3-3 Proteins); 0 (Biomarkers, Tumor); 0 (Ligands); 0 (Peptide Fragments); 0 (Peptide Library); 0 (Protein Isoforms); 0 (Recombinant Fusion Proteins); 0 (Recombinant Proteins); 0 (TAZ protein, human); 0 (Transcription Factors); EC 3.1.- (Exoribonucleases); EC 3.1.- (SFN protein, human)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170811
[Lr] Data última revisão:
170811
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170707
[St] Status:MEDLINE
[do] DOI:10.1021/acs.biochem.7b00153


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[PMID]:28666126
[Au] Autor:Graf M; Bonetti D; Lockhart A; Serhal K; Kellner V; Maicher A; Jolivet P; Teixeira MT; Luke B
[Ad] Endereço:Institute of Molecular Biology (IMB), 55128 Mainz, Germany.
[Ti] Título:Telomere Length Determines TERRA and R-Loop Regulation through the Cell Cycle.
[So] Source:Cell;170(1):72-85.e14, 2017 Jun 29.
[Is] ISSN:1097-4172
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Maintenance of a minimal telomere length is essential to prevent cellular senescence. When critically short telomeres arise in the absence of telomerase, they can be repaired by homology-directed repair (HDR) to prevent premature senescence onset. It is unclear why specifically the shortest telomeres are targeted for HDR. We demonstrate that the non-coding RNA TERRA accumulates as HDR-promoting RNA-DNA hybrids (R-loops) preferentially at very short telomeres. The increased level of TERRA and R-loops, exclusively at short telomeres, is due to a local defect in RNA degradation by the Rat1 and RNase H2 nucleases, respectively. Consequently, the coordination of TERRA degradation with telomere replication is altered at shortened telomeres. R-loop persistence at short telomeres contributes to activation of the DNA damage response (DDR) and promotes recruitment of the Rad51 recombinase. Thus, the telomere length-dependent regulation of TERRA and TERRA R-loops is a critical determinant of the rate of replicative senescence.
[Mh] Termos MeSH primário: Ciclo Celular
Saccharomyces cerevisiae/citologia
Saccharomyces cerevisiae/metabolismo
Telômero/metabolismo
[Mh] Termos MeSH secundário: Senescência Celular
Dano ao DNA
Exorribonucleases/metabolismo
Hibridização de Ácido Nucleico
Reparo de DNA por Recombinação
Proteínas Repressoras/metabolismo
Saccharomyces cerevisiae/genética
Proteínas de Saccharomyces cerevisiae/metabolismo
Telômero/química
Proteínas de Ligação a Telômeros/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RIF2 protein, S cerevisiae); 0 (Repressor Proteins); 0 (Saccharomyces cerevisiae Proteins); 0 (Telomere-Binding Proteins); 146589-82-4 (RIF1 protein, S cerevisiae); 147883-15-6 (RAT1 protein, S cerevisiae); EC 3.1.- (Exoribonucleases)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170701
[St] Status:MEDLINE



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