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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/27916754/-autoantibodies-of-inflammatory-myopathies-update
#2
Shigeaki Suzuki
Inflammatory myopathies are a heterogeneous group of immune-mediated diseases that involve the skeletal muscle as well as many other organs. In addition to a histological diagnosis at muscle biopsy, the clinical phenotypes of inflammatory myopathies can be defined by the presence of various autoantibodies that are originally detected by RNA or protein immunoprecipitation. However, the correlation between histological features and autoantibodies has not been fully elucidated. Immune-mediated necrotizing myopathy (IMNM), which is characterized by significant necrotic and regeneration muscle fibers with minimal or no inflammatory cell infiltration, is associated with the presence of autoantibodies...
December 2016: Brain and Nerve, Shinkei Kenkyū No Shinpo
https://www.readbyqxmd.com/read/27913733/identification-of-2-methylthio-cyclic-n6-threonylcarbamoyladenosine-ms2ct6a-as-a-novel-rna-modification-at-position-37-of-trnas
#3
Byeong-Il Kang, Kenjyo Miyauchi, Michal Matuszewski, Gabriel Silveira D'Almeida, Mary Anne T Rubio, Juan D Alfonzo, Kazuki Inoue, Yuriko Sakaguchi, Takeo Suzuki, Elzbieta Sochacka, Tsutomu Suzuki
Transfer RNA modifications play pivotal roles in protein synthesis. N(6)-threonylcarbamoyladenosine (t(6)A) and its derivatives are modifications found at position 37, 3'-adjacent to the anticodon, in tRNAs responsible for ANN codons. These modifications are universally conserved in all domains of life. t(6)A and its derivatives have pleiotropic functions in protein synthesis including aminoacylation, decoding and translocation. We previously discovered a cyclic form of t(6)A (ct(6)A) as a chemically labile derivative of t(6)A in tRNAs from bacteria, fungi, plants and protists...
December 2, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27911835/two-crystal-structures-reveal-design-for-repurposing-the-c-ala-domain-of-human-alars
#4
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/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/27899648/genetic-selection-for-mistranslation-rescues-a-defective-co-chaperone-in-yeast
#7
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/27889804/quest-for-ancestors-of-eukaryal-cells-based-on-phylogenetic-analyses-of-aminoacyl-trna-synthetases
#8
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
#9
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/27887987/structural-characterization-of-human-aminoacyl-trna-synthetases-for-translational-and-nontranslational-functions
#10
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
#11
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/27879432/induced-fit-of-the-peptidyl-transferase-center-of-the-ribosome-and-conformational-freedom-of-the-esterified-amino-acids
#12
Jean Lehmann
The catalytic site of most enzymes can efficiently handle only one substrate. In contrast, the ribosome is capable of polymerizing at a similar rate at least 20 different kinds of amino acids from aminoacyl-tRNA carriers while using just one catalytic site, the peptidyl-transferase center (PTC). An induced-fit mechanism has been uncovered in the PTC, but a possible connection between this mechanism and the uniform handling of the substrates has not been investigated. We present an analysis of published ribosome structures supporting the hypothesis that the induced-fit eliminates unreactive rotamers predominantly populated for some A-site aminoacyl esters before induction...
November 22, 2016: RNA
https://www.readbyqxmd.com/read/27876679/predicting-the-pathogenicity-of-aminoacyl-trna-synthetase-mutations
#13
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
#14
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/27872201/identification-of-chemical-compounds-that-inhibit-protein-synthesis-in-pseudomonas-aeruginosa
#15
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
#16
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/27863242/decoding-mammalian-ribosome-mrna-states-by-translational-gtpase-complexes
#17
Sichen Shao, Jason Murray, Alan Brown, Jack Taunton, V Ramakrishnan, Ramanujan S Hegde
In eukaryotes, accurate protein synthesis relies on a family of translational GTPases that pair with specific decoding factors to decipher the mRNA code on ribosomes. We present structures of the mammalian ribosome engaged with decoding factor⋅GTPase complexes representing intermediates of translation elongation (aminoacyl-tRNA⋅eEF1A), termination (eRF1⋅eRF3), and ribosome rescue (Pelota⋅Hbs1l). Comparative analyses reveal that each decoding factor exploits the plasticity of the ribosomal decoding center to differentially remodel ribosomal proteins and rRNA...
November 17, 2016: Cell
https://www.readbyqxmd.com/read/27849601/rna-modification-enzyme-trub-is-a-trna-chaperone
#18
Laura Carole Keffer-Wilkes, Govardhan Reddy Veerareddygari, Ute Kothe
Cellular RNAs are chemically modified by many RNA modification enzymes; however, often the functions of modifications remain unclear, such as for pseudouridine formation in the tRNA TΨC arm by the bacterial tRNA pseudouridine synthase TruB. Here we test the hypothesis that RNA modification enzymes also act as RNA chaperones. Using TruB as a model, we demonstrate that TruB folds tRNA independent of its catalytic activity, thus increasing the fraction of tRNA that can be aminoacylated. By rapid kinetic stopped-flow analysis, we identified the molecular mechanism of TruB's RNA chaperone activity: TruB binds and unfolds both misfolded and folded tRNAs thereby providing misfolded tRNAs a second chance at folding...
November 14, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27847344/assessing-the-effects-of-threonyl-trna-synthetase-on-angiogenesis-related-responses
#19
Adam C Mirando, Khadar Abdi, Peibin Wo, Karen M Lounsbury
Several recent reports have found a connection between specific aminoacyl-tRNA synthetases and the regulation of angiogenesis. As this new area of research is explored, it is important to have reliable assays to assess the specific angiogenesis functions of these enzymes. This review provides information about specific in vitro and in vivo methods that were used to assess the angiogenic functions of threonyl-tRNA synthetase including endothelial cell migration and tube assays as well as chorioallantoic membrane and tumor vascularization assays...
November 12, 2016: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/27837480/in-vivo-photo-cross-linking-to-study-t3s-interactions-demonstrated-using-the-yersinia-pestis-t3s-system
#20
Thomas A Henderson, Matthew L Nilles
Cross-linking of proteins is effective in determining protein-protein interactions. The use of photo-cross-linkers was developed to study protein interactions in several manners. One method involved the incorporation of photo-activatable cross-linking groups into chemically synthesized peptides. A second approach relies on incorporation of photo-activatable cross-linking groups into proteins using tRNAs with chemically bound photo-activatable amino acids with suppressor tRNAs translational systems to incorporate the tags into specific sites...
2017: Methods in Molecular Biology
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