Base de dados : MEDLINE
Pesquisa : G02.111.012.055 [Categoria DeCS]
Referências encontradas : 355 [refinar]
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[PMID]:28918092
[Au] Autor:Ferro I; Liebeton K; Ignatova Z
[Ad] Endereço:Biochemistry and Molecular Biology, Department of Chemistry, University of Hamburg, Hamburg, Germany.
[Ti] Título:Growth-Rate Dependent Regulation of tRNA Level and Charging in Bacillus licheniformis.
[So] Source:J Mol Biol;429(20):3102-3112, 2017 Oct 13.
[Is] ISSN:1089-8638
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Cellular growth crucially depends on protein synthesis and the abundance of translational components. Among them, aminoacyl-tRNAs play a central role in biosynthesis and shape the kinetics of mRNA translation, thus influencing protein production. Here, we used microarray-based approaches to determine the charging levels and tRNA abundance of Bacillus licheniformis. We observed an interesting cross-talk among tRNA expression, charging pattern, and growth rate. For a large subset of tRNAs, we found a co-regulated and augmented expression at high growth rate. Their tRNA aminoacylation level is kept relatively constant through riboswitch-regulated expression of the cognate aminoacyl-tRNA-synthetase (AARS). We show that AARSs with putative riboswitch-controlled expression are those charging tRNAs with amino acids which disfavor cell growth when individually added to the nutrient medium. Our results suggest that the riboswitch-regulated AARS expression in B. licheniformis is a powerful mechanism not only to maintain a constant ratio of aminoacyl-tRNA independent of the growth rate but concomitantly to control the intracellular level of free amino acids.
[Mh] Termos MeSH primário: Aminoacilação
Bacillus licheniformis/crescimento & desenvolvimento
Bacillus licheniformis/metabolismo
Regulação Bacteriana da Expressão Gênica
RNA de Transferência/metabolismo
[Mh] Termos MeSH secundário: Perfilação da Expressão Gênica
Análise em Microsséries
Riboswitch
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Riboswitch); 9014-25-9 (RNA, Transfer)
[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:170918
[St] Status:MEDLINE


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[PMID]:28801462
[Au] Autor:Jank T; Belyi Y; Wirth C; Rospert S; Hu Z; Dengjel J; Tzivelekidis T; Andersen GR; Hunte C; Schlosser A; Aktories K
[Ad] Endereço:From the Institute for Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany, thomas.jank@pharmakol.uni-freiburg.de.
[Ti] Título:Protein glutaminylation is a yeast-specific posttranslational modification of elongation factor 1A.
[So] Source:J Biol Chem;292(39):16014-16023, 2017 Sep 29.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Ribosomal translation factors are fundamental for protein synthesis and highly conserved in all kingdoms of life. The essential eukaryotic elongation factor 1A (eEF1A) delivers aminoacyl tRNAs to the A-site of the translating 80S ribosome. Several studies have revealed that eEF1A is posttranslationally modified. Using MS analysis, site-directed mutagenesis, and X-ray structural data analysis of eEF1A, we identified a posttranslational modification in which the α amino group of mono-l-glutamine is covalently linked to the side chain of glutamate 45 in eEF1A. The MS analysis suggested that all eEF1A molecules are modified by this glutaminylation and that this posttranslational modification occurs at all stages of yeast growth. The mutational studies revealed that this glutaminylation is not essential for the normal functions of eEF1A in However, eEF1A glutaminylation slightly reduced growth under antibiotic-induced translational stress conditions. Moreover, we identified the same posttranslational modification in eEF1A from but not in various other eukaryotic organisms tested despite strict conservation of the Glu residue among these organisms. We therefore conclude that eEF1A glutaminylation is a yeast-specific posttranslational modification that appears to influence protein translation.
[Mh] Termos MeSH primário: Glutamina/metabolismo
Modelos Moleculares
Fator 1 de Elongação de Peptídeos/metabolismo
Processamento de Proteína Pós-Traducional
Proteínas de Saccharomyces cerevisiae/metabolismo
Saccharomyces cerevisiae/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Substituição de Aminoácidos
Aminoacilação/efeitos dos fármacos
Anti-Infecciosos/farmacologia
Sequência Conservada
Cristalografia por Raios X
Bases de Dados de Proteínas
Regulação Fúngica da Expressão Gênica/efeitos dos fármacos
Ácido Glutâmico/metabolismo
Sequências Hélice-Alça-Hélice
Mutagênese Sítio-Dirigida
Mutação
Fator 1 de Elongação de Peptídeos/química
Fator 1 de Elongação de Peptídeos/genética
Processamento de Proteína Pós-Traducional/efeitos dos fármacos
Proteínas Recombinantes de Fusão/química
Proteínas Recombinantes de Fusão/metabolismo
Saccharomyces cerevisiae/efeitos dos fármacos
Saccharomyces cerevisiae/crescimento & desenvolvimento
Proteínas de Saccharomyces cerevisiae/química
Proteínas de Saccharomyces cerevisiae/genética
Alinhamento de Sequência
Especificidade da Espécie
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Infective Agents); 0 (Peptide Elongation Factor 1); 0 (Recombinant Fusion Proteins); 0 (Saccharomyces cerevisiae Proteins); 0 (TEF2 protein, S cerevisiae); 0RH81L854J (Glutamine); 3KX376GY7L (Glutamic Acid)
[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:170813
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.801035


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[PMID]:28632987
[Au] Autor:Abbott JA; Guth E; Kim C; Regan C; Siu VM; Rupar CA; Demeler B; Francklyn CS; Robey-Bond SM
[Ad] Endereço:Department of Biochemistry, University of Vermont , Burlington, Vermont 05405, United States.
[Ti] Título:The Usher Syndrome Type IIIB Histidyl-tRNA Synthetase Mutation Confers Temperature Sensitivity.
[So] Source:Biochemistry;56(28):3619-3631, 2017 Jul 18.
[Is] ISSN:1520-4995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Histidyl-tRNA synthetase (HARS) is a highly conserved translation factor that plays an essential role in protein synthesis. HARS has been implicated in the human syndromes Charcot-Marie-Tooth (CMT) Type 2W and Type IIIB Usher (USH3B). The USH3B mutation, which encodes a Y454S substitution in HARS, is inherited in an autosomal recessive fashion and associated with childhood deafness, blindness, and episodic hallucinations during acute illness. The biochemical basis of the pathophysiologies linked to USH3B is currently unknown. Here, we present a detailed functional comparison of wild-type (WT) and Y454S HARS enzymes. Kinetic parameters for enzymes and canonical substrates were determined using both steady state and rapid kinetics. Enzyme stability was examined using differential scanning fluorimetry. Finally, enzyme functionality in a primary cell culture was assessed. Our results demonstrate that the Y454S substitution leaves HARS amino acid activation, aminoacylation, and tRNA binding functions largely intact compared with those of WT HARS, and the mutant enzyme dimerizes like the wild type does. Interestingly, during our investigation, it was revealed that the kinetics of amino acid activation differs from that of the previously characterized bacterial HisRS. Despite the similar kinetics, differential scanning fluorimetry revealed that Y454S is less thermally stable than WT HARS, and cells from Y454S patients grown at elevated temperatures demonstrate diminished levels of protein synthesis compared to those of WT cells. The thermal sensitivity associated with the Y454S mutation represents a biochemical basis for understanding USH3B.
[Mh] Termos MeSH primário: Histidina-tRNA Ligase/genética
Histidina-tRNA Ligase/metabolismo
Mutação Puntual
Síndromes de Usher/enzimologia
Síndromes de Usher/genética
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Aminoacilação
Células Cultivadas
Estabilidade Enzimática
Células HEK293
Histidina-tRNA Ligase/química
Seres Humanos
Cinética
Modelos Moleculares
Biossíntese de Proteínas
RNA de Transferência/metabolismo
Alinhamento de Sequência
Temperatura Ambiente
Síndromes de Usher/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
9014-25-9 (RNA, Transfer); EC 6.1.1.21 (Histidine-tRNA Ligase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170804
[Lr] Data última revisão:
170804
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170621
[St] Status:MEDLINE
[do] DOI:10.1021/acs.biochem.7b00114


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[PMID]:28586482
[Au] Autor:Evans ME; Clark WC; Zheng G; Pan T
[Ad] Endereço:Department of Biochemistry & Molecular Biology, University of Chicago, Chicago, IL 60637, USA.
[Ti] Título:Determination of tRNA aminoacylation levels by high-throughput sequencing.
[So] Source:Nucleic Acids Res;45(14):e133, 2017 Aug 21.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Transfer RNA (tRNA) decodes mRNA codons when aminoacylated (charged) with an amino acid at its 3' end. Charged tRNAs turn over rapidly in cells, and variations in charged tRNA fractions are known to be a useful parameter in cellular responses to stress. tRNA charging fractions can be measured for individual tRNA species using acid denaturing gels, or comparatively at the genome level using microarrays. These hybridization-based approaches cannot be used for high resolution analysis of mammalian tRNAs due to their large sequence diversity. Here we develop a high-throughput sequencing method that enables accurate determination of charged tRNA fractions at single-base resolution (Charged DM-tRNA-seq). Our method takes advantage of the recently developed DM-tRNA-seq method, but includes additional chemical steps that specifically remove the 3'A residue in uncharged tRNA. Charging fraction is obtained by counting the fraction of A-ending reads versus A+C-ending reads for each tRNA species in the same sequencing reaction. In HEK293T cells, most cytosolic tRNAs are charged at >80% levels, whereas tRNASer and tRNAThr are charged at lower levels. These low charging levels were validated using acid denaturing gels. Our method should be widely applicable for investigations of tRNA charging as a parameter in biological regulation.
[Mh] Termos MeSH primário: Sequenciamento de Nucleotídeos em Larga Escala/métodos
Aminoacil-RNA de Transferência/genética
RNA de Transferência/genética
Aminoacilação de RNA de Transferência/genética
[Mh] Termos MeSH secundário: Aminoacilação
Northern Blotting
Células HEK293
Seres Humanos
Modelos Genéticos
RNA de Transferência/metabolismo
Aminoacil-RNA de Transferência/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Transfer, Amino Acyl); 9014-25-9 (RNA, Transfer)
[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:170607
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx514


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[PMID]:28419689
[Au] Autor:Kartvelishvili E; Tworowski D; Vernon H; Moor N; Wang J; Wong LJ; Chrzanowska-Lightowlers Z; Safro M
[Ad] Endereço:Department of Structural Biology, Weizmann Institute of Science, Israel.
[Ti] Título:Kinetic and structural changes in HsmtPheRS, induced by pathogenic mutations in human FARS2.
[So] Source:Protein Sci;26(8):1505-1516, 2017 Aug.
[Is] ISSN:1469-896X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mutations in the mitochondrial aminoacyl-tRNA synthetases (mtaaRSs) can cause profound clinical presentations, and have manifested as diseases with very selective tissue specificity. To date most of the mtaaRS mutations could be phenotypically recognized, such that clinicians could identify the affected mtaaRS from the symptoms alone. Among the recently reported pathogenic variants are point mutations in FARS2 gene, encoding the human mitochondrial PheRS. Patient symptoms range from spastic paraplegia to fatal infantile Alpers encephalopathy. How clinical manifestations of these mutations relate to the changes in three-dimensional structures and kinetic characteristics remains unclear, although impaired aminoacylation has been proposed as possible etiology of diseases. Here, we report four crystal structures of HsmtPheRS mutants, and extensive MD simulations for wild-type and nine mutants to reveal the structural changes on dynamic trajectories of HsmtPheRS. Using steady-state kinetic measurements of phenylalanine activation and tRNA aminoacylation, we gained insight into the structural and kinetic effects of mitochondrial disease-related mutations in FARS2 gene.
[Mh] Termos MeSH primário: Esclerose Cerebral Difusa de Schilder/genética
Proteínas Mitocondriais/química
Mutação
Paraplegia/genética
Fenilalanina-tRNA Ligase/química
RNA de Transferência de Fenilalanina/química
[Mh] Termos MeSH secundário: Adolescente
Motivos de Aminoácidos
Aminoacilação
Sítios de Ligação
Pré-Escolar
Cristalografia por Raios X
Esclerose Cerebral Difusa de Schilder/diagnóstico
Esclerose Cerebral Difusa de Schilder/metabolismo
Esclerose Cerebral Difusa de Schilder/patologia
Feminino
Seres Humanos
Cinética
Masculino
Mitocôndrias/genética
Mitocôndrias/metabolismo
Mitocôndrias/patologia
Proteínas Mitocondriais/genética
Proteínas Mitocondriais/metabolismo
Simulação de Dinâmica Molecular
Paraplegia/diagnóstico
Paraplegia/metabolismo
Paraplegia/patologia
Fenilalanina-tRNA Ligase/genética
Fenilalanina-tRNA Ligase/metabolismo
Ligação Proteica
Conformação Proteica em alfa-Hélice
Conformação Proteica em Folha beta
Domínios e Motivos de Interação entre Proteínas
RNA de Transferência de Fenilalanina/metabolismo
Alinhamento de Sequência
Especificidade por Substrato
Termodinâmica
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Mitochondrial Proteins); 0 (RNA, Transfer, Phe); EC 6.1.1.20 (FARS2 protein, human); EC 6.1.1.20 (Phenylalanine-tRNA Ligase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170824
[Lr] Data última revisão:
170824
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170419
[St] Status:MEDLINE
[do] DOI:10.1002/pro.3176


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[PMID]:28335556
[Au] Autor:Goto-Ito S; Ito T; Yokoyama S
[Ad] Endereço:Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan. sakurako@iam.u-tokyo.ac.jp.
[Ti] Título:Trm5 and TrmD: Two Enzymes from Distinct Origins Catalyze the Identical tRNA Modification, m¹G37.
[So] Source:Biomolecules;7(1), 2017 Mar 21.
[Is] ISSN:2218-273X
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:The N¹-atom of guanosine at position 37 in transfer RNA (tRNA) is methylated by tRNA methyltransferase 5 (Trm5) in eukaryotes and archaea, and by tRNA methyltransferase D (TrmD) in bacteria. The resultant modified nucleotide m¹G37 positively regulates the aminoacylation of the tRNA, and simultaneously functions to prevent the +1 frameshift on the ribosome. Interestingly, Trm5 and TrmD have completely distinct origins, and therefore bear different tertiary folds. In this review, we describe the different strategies utilized by Trm5 and TrmD to recognize their substrate tRNAs, mainly based on their crystal structures complexed with substrate tRNAs.
[Mh] Termos MeSH primário: RNA de Transferência/metabolismo
tRNA Metiltransferases/metabolismo
[Mh] Termos MeSH secundário: Aminoacilação
Catálise
Cristalografia por Raios X
Modelos Moleculares
RNA de Transferência/química
Especificidade por Substrato
tRNA Metiltransferases/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
9014-25-9 (RNA, Transfer); EC 2.1.1.- (tRNA Methyltransferases)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171108
[Lr] Data última revisão:
171108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170325
[St] Status:MEDLINE


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[PMID]:28321488
[Au] Autor:Lee YH; Chang CP; Cheng YJ; Kuo YY; Lin YS; Wang CC
[Ad] Endereço:Department of Life Sciences, National Central University, Jungli District, Taoyuan, 32001, Taiwan.
[Ti] Título:Evolutionary gain of highly divergent tRNA specificities by two isoforms of human histidyl-tRNA synthetase.
[So] Source:Cell Mol Life Sci;74(14):2663-2677, 2017 Jul.
[Is] ISSN:1420-9071
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:The discriminator base N73 is a key identity element of tRNA . In eukaryotes, N73 is an "A" in cytoplasmic tRNA and a "C" in mitochondrial tRNA . We present evidence herein that yeast histidyl-tRNA synthetase (HisRS) recognizes both A73 and C73, but somewhat prefers A73 even within the context of mitochondrial tRNA . In contrast, humans possess two distinct yet closely related HisRS homologues, with one encoding the cytoplasmic form (with an extra N-terminal WHEP domain) and the other encoding its mitochondrial counterpart (with an extra N-terminal mitochondrial targeting signal). Despite these two isoforms sharing high sequence similarities (81% identity), they strongly preferred different discriminator bases (A73 or C73). Moreover, only the mitochondrial form recognized the anticodon as a strong identity element. Most intriguingly, swapping the discriminator base between the cytoplasmic and mitochondrial tRNA isoacceptors conveniently switched their enzyme preferences. Similarly, swapping seven residues in the active site between the two isoforms readily switched their N73 preferences. This study suggests that the human HisRS genes, while descending from a common ancestor with dual function for both types of tRNA , have acquired highly specialized tRNA recognition properties through evolution.
[Mh] Termos MeSH primário: Evolução Molecular
Histidina-tRNA Ligase/metabolismo
RNA de Transferência/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Aminoacilação
Bacillus subtilis/enzimologia
Escherichia coli/enzimologia
Histidina-tRNA Ligase/química
Seres Humanos
Isoenzimas/química
Isoenzimas/metabolismo
Mitocôndrias/metabolismo
Proteínas Mutantes/metabolismo
Filogenia
Saccharomyces cerevisiae/enzimologia
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Isoenzymes); 0 (Mutant Proteins); 9014-25-9 (RNA, Transfer); EC 6.1.1.21 (Histidine-tRNA Ligase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170915
[Lr] Data última revisão:
170915
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170322
[St] Status:MEDLINE
[do] DOI:10.1007/s00018-017-2491-3


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[PMID]:28119416
[Au] Autor:Martinez A; Yamashita S; Nagaike T; Sakaguchi Y; Suzuki T; Tomita K
[Ad] Endereço:Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba 277-8562, Japan.
[Ti] Título:Human BCDIN3D monomethylates cytoplasmic histidine transfer RNA.
[So] Source:Nucleic Acids Res;45(9):5423-5436, 2017 May 19.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Human RNA methyltransferase BCDIN3D is overexpressed in breast cancer cells, and is related to the tumorigenic phenotype and poor prognosis of breast cancer. Here, we show that cytoplasmic tRNAHis is the primary target of BCDIN3D in human cells. Recombinant human BCDIN3D, expressed in Escherichia coli, monomethylates the 5΄-monophosphate of cytoplasmic tRNAHis efficiently in vitro. In BCDN3D-knockout cells, established by CRISPR/Cas9 editing, the methyl moiety at the 5΄-monophosphate of cytoplasmic tRNAHis is lost, and the exogenous expression of BCDIN3D in the knockout cells restores the modification in cytoplasmic tRNAHis. BCIDN3D recognizes the 5΄-guanosine nucleoside at position -1 (G-1) and the eight-nucleotide acceptor helix with the G-1-A73 mis-pair at the top of the acceptor stem of cytoplasmic tRNAHis, which are exceptional structural features among cytoplasmic tRNA species. While the monomethylation of the 5΄-monophosphate of cytoplasmic tRNAHis affects neither the overall aminoacylation process in vitro nor the steady-state level of cytoplasmic tRNAHisin vivo, it protects the cytoplasmic tRNAHis transcript from degradation in vitro. Thus, BCDIN3D acts as a cytoplasmic tRNAHis-specific 5΄-methylphosphate capping enzyme. The present results also suggest the possible involvement of the monomethylation of the 5΄-monophosphate of cytoplasmic tRNAHis and/or cytoplasmic tRNAHis itself in the tumorigenesis of breast cancer cells.
[Mh] Termos MeSH primário: Metiltransferases/metabolismo
RNA de Transferência de Histidina/metabolismo
[Mh] Termos MeSH secundário: Aminoacilação
Sequência de Bases
Citoplasma/metabolismo
Células HEK293
Seres Humanos
Metilação
Conformação de Ácido Nucleico
Estabilidade de RNA
RNA de Transferência de Histidina/química
RNA de Transferência de Histidina/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Transfer, His); EC 2.1.1.- (BCDIN3D protein, human); EC 2.1.1.- (Methyltransferases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170919
[Lr] Data última revisão:
170919
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170126
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx051


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[PMID]:28049726
[Au] Autor:Meng F; Cang X; Peng Y; Li R; Zhang Z; Li F; Fan Q; Guan AS; Fischel-Ghosian N; Zhao X; Guan MX
[Ad] Endereço:From the Division of Medical Genetics and Genomics, Zhejiang Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
[Ti] Título:Biochemical Evidence for a Nuclear Modifier Allele (A10S) in TRMU (Methylaminomethyl-2-thiouridylate-methyltransferase) Related to Mitochondrial tRNA Modification in the Phenotypic Manifestation of Deafness-associated 12S rRNA Mutation.
[So] Source:J Biol Chem;292(7):2881-2892, 2017 Feb 17.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Nuclear modifier gene(s) was proposed to modulate the phenotypic expression of mitochondrial DNA mutation(s). Our previous investigations revealed that a nuclear modifier allele (A10S) in TRMU (methylaminomethyl-2-thiouridylate-methyltransferase) related to tRNA modification interacts with 12S rRNA 1555A→G mutation to cause deafness. The A10S mutation resided at a highly conserved residue of the N-terminal sequence. It was hypothesized that the A10S mutation altered the structure and function of TRMU, thereby causing mitochondrial dysfunction. Using molecular dynamics simulations, we showed that the A10S mutation introduced the Ser dynamic electrostatic interaction with the Lys residue of helix 4 within the catalytic domain of TRMU. The Western blotting analysis displayed the reduced levels of TRMU in mutant cells carrying the A10S mutation. The thermal shift assay revealed the value of mutant TRMU protein, lower than that of the wild-type counterpart. The A10S mutation caused marked decreases in 2-thiouridine modification of U34 of tRNA , tRNA and tRNA However, the A10S mutation mildly increased the aminoacylated efficiency of tRNAs. The altered 2-thiouridine modification worsened the impairment of mitochondrial translation associated with the m.1555A→G mutation. The defective translation resulted in the reduced activities of mitochondrial respiration chains. The respiratory deficiency caused the reduction of mitochondrial ATP production and elevated the production of reactive oxidative species. As a result, mutated TRMU worsened mitochondrial dysfunctions associated with m.1555A→G mutation, exceeding the threshold for expressing a deafness phenotype. Our findings provided new insights into the pathophysiology of maternally inherited deafness that was manifested by interaction between mtDNA mutation and nuclear modifier gene.
[Mh] Termos MeSH primário: Alelos
Surdez/genética
Mitocôndrias/metabolismo
Proteínas Mitocondriais/metabolismo
Mutação
Fenótipo
RNA Ribossômico/genética
RNA de Transferência/metabolismo
tRNA Metiltransferases/metabolismo
[Mh] Termos MeSH secundário: Aminoacilação
Estabilidade Enzimática
Fluorometria
Seres Humanos
Proteínas Mitocondriais/genética
Simulação de Dinâmica Molecular
tRNA Metiltransferases/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Mitochondrial Proteins); 0 (RNA, Ribosomal); 0 (RNA, ribosomal, 12S); 9014-25-9 (RNA, Transfer); EC 2.1.1.- (tRNA Methyltransferases); EC 2.1.1.61 (TRMU protein, human)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170628
[Lr] Data última revisão:
170628
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170105
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M116.749374


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[PMID]:28040467
[Au] Autor:Magalhães S; Aroso M; Roxo I; Ferreira S; Cerveira F; Ramalheira E; Ferreira R; Vitorino R
[Ad] Endereço:QOPNA, Mass Spectrometry Center, Department of Chemistry, University of Aveiro, Aveiro, Portugal; iBiMED - Institute for Biomedicine, University of Aveiro, Aveiro, Portugal.
[Ti] Título:Proteomic profile of susceptible and multidrug-resistant clinical isolates of Escherichia coli and Klebsiella pneumoniae using label-free and immunoproteomic strategies.
[So] Source:Res Microbiol;168(3):222-233, 2017 Apr.
[Is] ISSN:1769-7123
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Infectious diseases caused by multidrug-resistant (MDR) Enterobacteriaceae have exponentially increased in the past decade, and are a major concern in hospitals. In the first part of the work, we compared the proteome profile of MDR and susceptible clinical isolates of Escherichia coli and Klebsiella pneumoniae in order to identify possible biological processes associated with drug resistance and susceptible phenotypes, using a label-free approach. In the second part, we used an immunoproteomics approach to identify immunoreactive proteins in the same isolates. A total of 388 and 377 proteins were identified in MDR and susceptible E. coli, respectively, evidencing that biological processes related to translation are upregulated in E. coli MDR, while there is an upregulation of processes related to catalytic activity in K. pneumoniae MDR. Both MDR strains show downregulation of processes related to amino acid activation and tRNA amino-acylation. Our data also suggest that MDR strains have higher immunoreactivity than the susceptible strains. The application of high-throughput mass spectrometry (MS) and bioinformatics to the study of modulation of biological processes might shed light on the characterization of multidrug resistance in bacteria.
[Mh] Termos MeSH primário: Proteínas de Bactérias/imunologia
Proteínas de Bactérias/isolamento & purificação
Farmacorresistência Bacteriana Múltipla/genética
Escherichia coli/genética
Escherichia coli/metabolismo
Klebsiella pneumoniae/genética
Proteômica/métodos
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Aminoacilação
Proteínas de Bactérias/metabolismo
Escherichia coli/efeitos dos fármacos
Escherichia coli/imunologia
Infecções por Escherichia coli/microbiologia
Feminino
Seres Humanos
Infecções por Klebsiella/microbiologia
Klebsiella pneumoniae/efeitos dos fármacos
Klebsiella pneumoniae/imunologia
Masculino
Espectrometria de Massas
Testes de Sensibilidade Microbiana
Meia-Idade
RNA de Transferência
Regulação para Cima
beta-Lactamases/biossíntese
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 9014-25-9 (RNA, Transfer); EC 3.5.2.6 (beta-Lactamases)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170413
[Lr] Data última revisão:
170413
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170102
[St] Status:MEDLINE



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