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tRNA Synthetase

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https://www.readbyqxmd.com/read/27918435/piecemeal-buildup-of-the-genetic-code-ribosomes-and-genomes-from-primordial-trna-building-blocks
#1
Derek Caetano-Anollés, Gustavo Caetano-Anollés
The origin of biomolecular machinery likely centered around an ancient and central molecule capable of interacting with emergent macromolecular complexity. tRNA is the oldest and most central nucleic acid molecule of the cell. Its co-evolutionary interactions with aminoacyl-tRNA synthetase protein enzymes define the specificities of the genetic code and those with the ribosome their accurate biosynthetic interpretation. Phylogenetic approaches that focus on molecular structure allow reconstruction of evolutionary timelines that describe the history of RNA and protein structural domains...
December 2, 2016: Life
https://www.readbyqxmd.com/read/27913726/competitive-binding-between-seryl-trna-synthetase-yy1-complex-and-nfkb1-at-the-distal-segment-results-in-differential-regulation-of-human-vegfa-promoter-activity-during-angiogenesis
#2
Chuan-Yang Fu, Po-Chun Wang, Huai-Jen Tsai
Vascular endothelial growth factor (VEGF) plays a pivotal role in angiogenesis. Previous studies focused on transcriptional regulation modulated by proximal upstream cis-regulatory elements (CREs) of the human vegfa promoter. However, we hypothesized that distal upstream CREs may also be involved in controlling vegfa transcription. In this study, we found that the catalytic domain of Seryl-tRNA synthetase (SerRS) interacted with transcription factor Yin Yang 1 (YY1) to form a SerRS/YY1 complex that negatively controls vegfa promoter activity through binding distal CREs at -4654 to -4623 of vegfa Particularly, we demonstrated that the -4654 to -4623 segment, which predominantly controls vegfa promoter activity, is involved in competitive binding between SerRS/YY1 complex and NFKB1...
December 1, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27911835/two-crystal-structures-reveal-design-for-repurposing-the-c-ala-domain-of-human-alars
#3
Litao Sun, Youngzee Song, David Blocquel, Xiang-Lei Yang, Paul Schimmel
The 20 aminoacyl tRNA synthetases (aaRSs) couple each amino acid to their cognate tRNAs. During evolution, 19 aaRSs expanded by acquiring novel noncatalytic appended domains, which are absent from bacteria and many lower eukaryotes but confer extracellular and nuclear functions in higher organisms. AlaRS is the single exception, with an appended C-terminal domain (C-Ala) that is conserved from prokaryotes to humans but with a wide sequence divergence. In human cells, C-Ala is also a splice variant of AlaRS...
November 28, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27908233/procedure-for-purification-of-recombinant-premsk1p-from-e-coli-determines-its-properties-as-a-factor-of-trna-import-into-yeast-mitochondria
#4
E V Smirnova, I V Chicherin, M V Baleva, N S Entelis, I A Tarassov, P A Kamenski
Mitochondrial genomes of many eukaryotic organisms do not code for the full tRNA set necessary for organellar translation. Missing tRNA species are imported from the cytosol. In particular, one out of two cytosolic lysine tRNAs of the yeast Saccharomyces cerevisiae is partially internalized by mitochondria. The key protein factor of this process is the precursor of mitochondrial lysyl-tRNA synthetase, preMsk1p. In this work, we show that recombinant preMsk1p purified from E. coli in native conditions, when used in an in vitro tRNA import system, demonstrates some properties different from those shown by the renatured protein purified from E...
October 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/27906773/suppression-of-aimp1-protects-cognition-in-alzheimer-s-disease-model-mice-3xtg-ad
#5
Sooah Jang, Jung Ho Lee, Bo Kyung Sohn, Eosu Kim, Sang Gyu Park, Kang Jun Yoon, Minsun Park, Eun Woo Kim, Jihyeon Jeong, Jun-Young Lee, Chul Hoon Kim, Kee Namkoong
Neuroinflammation has been raised as a candidate of unifying pathogenesis and a target of a disease-modifying strategy for Alzheimer's disease (AD). Aminoacyl-tRNA synthetase complex (ARS)-interacting multifunctional protein 1 (AIMP1) is a cytokine that is known to amplify the actions of tumor necrosis factor-α and to be involved in microglial activation and neuronal death. In this respect, AIMP1 could be a plausible target for the treatment of AD. Therefore, we aimed to examine whether anti-AIMP1 antibody could exert therapeutic effects against cognitive impairment using 3xTg-AD mice...
November 30, 2016: Neuroreport
https://www.readbyqxmd.com/read/27903912/the-complex-evolutionary-history-of-aminoacyl-trna-synthetases
#6
Anargyros Chaliotis, Panayotis Vlastaridis, Dimitris Mossialos, Michael Ibba, Hubert D Becker, Constantinos Stathopoulos, Grigorios D Amoutzias
Aminoacyl-tRNA synthetases (AARSs) are a superfamily of enzymes responsible for the faithful translation of the genetic code and have lately become a prominent target for synthetic biologists. Our large-scale analysis of >2500 prokaryotic genomes reveals the complex evolutionary history of these enzymes and their paralogs, in which horizontal gene transfer played an important role. These results show that a widespread belief in the evolutionary stability of this superfamily is misconceived. Although AlaRS, GlyRS, LeuRS, IleRS, ValRS are the most stable members of the family, GluRS, LysRS and CysRS often have paralogs, whereas AsnRS, GlnRS, PylRS and SepRS are often absent from many genomes...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27903248/long-term-clinical-course-of-anti-glycyl-trna-synthetase-anti-ej-antibody-related-interstitial-lung-disease-pathologically-proven-by-surgical-lung-biopsy
#7
Hajime Sasano, Eri Hagiwara, Hideya Kitamura, Yasunori Enomoto, Norikazu Matsuo, Tomohisa Baba, Shinichiro Iso, Koji Okudela, Tae Iwasawa, Shinji Sato, Yasuo Suzuki, Tamiko Takemura, Takashi Ogura
BACKGROUND: Anti-glycyl-tRNA synthetase (anti-EJ) antibody is occasionally positive in patients with interstitial lung disease (ILD). We aimed to define the clinical, radiological and pathological features of patients with anti-EJ antibody-positive ILD (EJ-ILD). METHODS: We retrospectively analyzed the medical records of 12 consecutive patients with EJ-ILD who underwent surgical lung biopsy. RESULTS: The median follow-up time was 74 months (range, 17-115 months)...
December 1, 2016: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/27899648/genetic-selection-for-mistranslation-rescues-a-defective-co-chaperone-in-yeast
#8
Kyle S Hoffman, Matthew D Berg, Brian H Shilton, Christopher J Brandl, Patrick O'Donoghue
Despite the general requirement for translation fidelity, mistranslation can be an adaptive response. We selected spontaneous second site mutations that suppress the stress sensitivity caused by a Saccharomyces cerevisiae tti2 allele with a Leu to Pro mutation at residue 187, identifying a single nucleotide mutation at the same position (C70U) in four tRNA(Pro)UGG genes. Linkage analysis and suppression by SUF9G3:U70 expressed from a centromeric plasmid confirmed the causative nature of the suppressor mutation...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27891590/bi-allelic-iars-mutations-in-a-child-with-intra-uterine-growth-retardation-neonatal-cholestasis-and-mild-developmental-delay
#9
Naama Orenstein, Karin Weiss, Stephanie N Oprescu, Rivka Shapira, Dvora Kidron, Lina Vanagaite-Basel, Anthony Antonellis, Maximilian Muenke
Recently, bi-allelic mutations in cytosolic isoleucyl-tRNA synthetase (IARS) have been described in three individuals with growth delay, hepatic dysfunction, and neurodevelopmental disabilities. Here we report an additional subject with this condition identified by whole-exome sequencing. Our findings support the association between this disorder and neonatal cholestasis with distinct liver pathology. Furthermore, we provide functional data on two novel missense substitutions and expand the phenotype to include mild developmental delay, skin hyper-elasticity, and hypervitaminosis D...
November 28, 2016: Clinical Genetics
https://www.readbyqxmd.com/read/27889804/quest-for-ancestors-of-eukaryal-cells-based-on-phylogenetic-analyses-of-aminoacyl-trna-synthetases
#10
Ryutaro Furukawa, Mizuho Nakagawa, Takuya Kuroyanagi, Shin-Ichi Yokobori, Akihiko Yamagishi
The three-domain phylogenetic system of life has been challenged, particularly with regard to the position of Eukarya. The recent increase of known genome sequences has allowed phylogenetic analyses of all extant organisms using concatenated sequence alignment of universally conserved genes; these data supported the two-domain hypothesis, which place eukaryal species as ingroups of the Domain Archaea. However, the origin of Eukarya is complicated: the closest archaeal species to Eukarya differs in single-gene phylogenetic analyses depending on the genes...
November 26, 2016: Journal of Molecular Evolution
https://www.readbyqxmd.com/read/27888997/comprehensive-assessment-of-myositis-specific-autoantibodies-in-polymyositis-dermatomyositis-associated-interstitial-lung-disease
#11
Hironao Hozumi, Tomoyuki Fujisawa, Ran Nakashima, Takeshi Johkoh, Hiromitsu Sumikawa, Akihiro Murakami, Noriyuki Enomoto, Naoki Inui, Yutaro Nakamura, Yuji Hosono, Yoshitaka Imura, Tsuneyo Mimori, Takafumi Suda
OBJECTIVES: Myositis-specific autoantibodies (MSAs) are associated with clinical phenotypes in polymyositis/dermatomyositis (PM/DM). No study has investigated the clinical features based on comprehensive MSA assessment in PM/DM-associated interstitial lung disease (ILD). We aimed to determine the practical significance of MSAs in PM/DM-ILD. METHODS: Sixty consecutive PM/DM-ILD patients were retrospectively analysed. Serum MSAs were comprehensively measured using immunoprecipitation assay...
December 2016: Respiratory Medicine
https://www.readbyqxmd.com/read/27888605/natural-antisense-transcripts-are-linked-to-the-modulation-of-mitochondrial-function-and-teliospore-dormancy-in-ustilago-maydis
#12
Lauren A Ostrowski, Barry J Saville
The basidiomycete smut fungus Ustilago maydis causes common smut of corn. This disease is spread through the production of teliospores, which are thick-walled dormant structures characterized by low rates of respiration and metabolism. Teliospores are formed when the fungus grows within the plant, and the morphological steps involved in their formation have been described, but the molecular events leading to dormancy are not known. In U. maydis, natural antisense transcripts (NATs) can function to alter gene expression and many NATs have increased levels in the teliospore...
November 26, 2016: Molecular Microbiology
https://www.readbyqxmd.com/read/27887987/structural-characterization-of-human-aminoacyl-trna-synthetases-for-translational-and-nontranslational-functions
#13
REVIEW
Pengfei Fang, Min Guo
Aminoacyl-tRNA synthetases (aaRSs) are enzymes that function at the first step of translation, catalyzing the conjugation of amino acids to their cognate tRNAs for protein synthesis. While preserving this essential role, higher eukaryotic aaRSs, such as human cytoplasmic aaRSs, have developed other functions during evolution, including angiogenesis, inflammation, development, tumorigenesis, etc. These translational and non-translational functions of aaRSs are attractive targets for developing antibacterial, antifungal, anticancer agents and for treating other human diseases...
November 22, 2016: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/27887986/isolation-of-bacterial-compartments-to-track-movement-of-protein-synthesis-factors
#14
Hanchao Zhao, Susan Martinis
Aminoacyl-tRNA synthetases (AARS) comprise an enzyme family that generates and maintains pools of aminoacylated tRNAs, which serve as essential substrates for protein synthesis. Many protein synthesis factors, including tRNA and AARS also have non-canonical functions. Particularly in mammalian cells, alternate functions of AARSs have been associated with re-distribution in the cell to sites that are removed from translation. Sub-fractionation methods for E. coli were designed and optimized to carefully investigate re-localization of bacterial AARSs and tRNA that might aid in conferring alternate activities...
November 22, 2016: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/27876679/predicting-the-pathogenicity-of-aminoacyl-trna-synthetase-mutations
#15
REVIEW
Stephanie N Oprescu, Laurie B Griffin, Asim A Beg, Anthony Antonellis
Aminoacyl-tRNA synthetases (ARSs) are ubiquitously expressed, essential enzymes responsible for charging tRNA with cognate amino acids-the first step in protein synthesis. ARSs are required for protein translation in the cytoplasm and mitochondria of all cells. Surprisingly, mutations in 28 of the 37 nuclear-encoded human ARS genes have been linked to a variety of recessive and dominant tissue-specific disorders. Current data indicate that impaired enzyme function is a robust predictor of the pathogenicity of ARS mutations...
November 20, 2016: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/27876148/fc-specific-biotinylation-of-antibody-using-an-engineered-photoactivatable-z-biotin-and-its-biosensing-application
#16
Hong-Ming Yang, Ru-Meng Bao, Chang-Mei Yu, Yan-Na Lv, Wei-Fen Zhang, Jin-Bao Tang
The development of a site-specific and covalent attachment methodology is crucial for antibody-biotin conjugates to preserve the antigen-binding ability of antibodies and yield homogeneous products. In this study, an engineered photoactivatable Z-domain variant [an UV-active amino acid benzoylphenylalanine (Bpa) was genetically incorporated into the Z-domain] carrying one biotin molecule (ZBpa-Biotin) was prepared by employing aminoacyl-tRNA synthetase/suppressor tRNA and Avitag/BirA techniques. The site-specific and covalent attachment of IgG-biotin conjugates, viz...
January 1, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/27875839/severe-metabolic-acidosis-and-hepatopathy-due-to-leukoencephalopathy-with-thalamus-and-brainstem-involvement-and-high-lactate
#17
Elizabeth A Sellars, Tonya Balmakund, Katherine Bosanko, Brandi L Nichols, Stephen G Kahler, Yuri A Zarate
Leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL) is a recently described autosomal recessive mitochondrial disease characterized by early onset of neurological symptoms, a biphasic clinical course, and distinctive neuroimaging. Pathogenic variants in the EARS2 gene that encode for mitochondrial glutamyl-tRNA synthetase are responsible for LTBL. Here, we describe the clinical course of an infant diagnosed with an acute crisis of LTBL and severe liver disease. This article illustrates the utility of blood lactate quantification in addition to basic metabolic testing and brain imaging in a child with low tone and poor growth...
November 22, 2016: Neuropediatrics
https://www.readbyqxmd.com/read/27872201/identification-of-chemical-compounds-that-inhibit-protein-synthesis-in-pseudomonas-aeruginosa
#18
Stephanie O Palmer, Yanmei Hu, Megan Keniry, James M Bullard
Four inhibitory compounds were identified using a poly-uridylic acid (polyU) mRNA-directed aminoacylation/translation (A/T) protein synthesis system composed of phenylalanyl-tRNA synthetases (PheRS), ribosomes, and ribosomal factors from Pseudomonas aeruginosa in an in vitro screen of a synthetic compound library. The compounds were specific for inhibition of bacterial protein synthesis. In enzymatic assays, the compounds inhibited protein synthesis with IC50 values ranging from 20 to 60 μM. Minimum inhibitory concentrations (MICs) were determined in cultures for a panel of pathogenic organisms, including Enterococcus faecalis, Escherichia coli, Haemophilus influenzae, P...
November 21, 2016: Journal of Biomolecular Screening
https://www.readbyqxmd.com/read/27871331/association-of-dars-gene-polymorphisms-with-the-risk-of-isolated-ventricular-septal-defects-in-the-chinese-han-population
#19
Yu Feng, Runsen Chen, Xuming Mo
BACKGROUND: Ventricular septal defects (VSD) are the most common subtype of congenital heart defects (CHD) and are estimated to account for 20 to 30% of all cases of CHD. The etiology of isolated VSD remains poorly understood. Eight core aminoacyl-tRNA synthetases (ARSs) (EPRS, MARS, QARS, RARS, IARS, LARS, KARS, and DARS) combine with three nonenzymatic components to form a complex known as the multisynthetase complex (MSC). Four single nucleotide polymorphisms (SNPs) in EPRS have been reported to be associated with risks of CHD in Chinese populations...
November 21, 2016: Italian Journal of Pediatrics
https://www.readbyqxmd.com/read/27867276/ursolic-acid-a-natural-pentacylcic-triterpene-from-ochrosia-elliptica-and-its-role-in-the-management-of-certain-neglected-tropical-diseases
#20
Rola M Labib, Sherif S Ebada, Fadia S Youssef, Mohamed L Ashour, Samir A Ross
BACKGROUND: Leishmaniasis and African trypanosomiasis are recognized as the leading causes of mortality and morbidity with the greatest prevalence in the developing countries. They affect more than one billion of the poorest people on the globe. OBJECTIVE: To find a cheap, affordable, safe, and efficacious antileshmanial and antitrypanosomal natural drug and to elucidate its probable mode of action. MATERIALS AND METHODS: Phytochemical investigation of the non-polar fraction of the methanol extract of leaves of Ochrosia elliptica Labill...
October 2016: Pharmacognosy Magazine
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