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tRNA Synthetase

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https://www.readbyqxmd.com/read/28723566/genome-wide-rnai-screen-for-fat-regulatory-genes-in-c-%C3%A2-elegans-identifies-a-proteostasis-ampk-axis-critical-for-starvation-survival
#1
Christopher M Webster, Elizabeth C Pino, Christopher E Carr, Lianfeng Wu, Ben Zhou, Lucydalila Cedillo, Michael C Kacergis, Sean P Curran, Alexander A Soukas
Organisms must execute metabolic defenses to survive nutrient deprivation. We performed a genome-wide RNAi screen in Caenorhabditis elegans to identify fat regulatory genes indispensable for starvation resistance. Here, we show that opposing proteostasis pathways are principal determinants of starvation survival. Reduced function of cytoplasmic aminoacyl tRNA synthetases (ARS genes) increases fat mass and extends starvation survival, whereas reduced proteasomal function reduces fat and starvation survival. These opposing pathways converge on AMP-activated protein kinase (AMPK) as the critical effector of starvation defenses...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28720827/small-chaperons-and-autophagy-protected-neurons-from-necrotic-cell-death
#2
Ye Lei, Kai Liu, Lin Hou, Lianggong Ding, Yuhong Li, Lei Liu
Neuronal necrosis occurs during early phase of ischemic insult. However, our knowledge of neuronal necrosis is still inadequate. To study the mechanism of neuronal necrosis, we previously established a Drosophila genetic model of neuronal necrosis by calcium overloading through expression of a constitutively opened cation channel mutant. Here, we performed further genetic screens and identified a suppressor of neuronal necrosis, CG17259, which encodes a seryl-tRNA synthetase. We found that loss-of-function (LOF) CG17259 activated eIF2α phosphorylation and subsequent up-regulation of chaperons (Hsp26 and Hsp27) and autophagy...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720599/hyperacute-muscle-weakness-in-an-unusual-coexistence-of-antisignal-recognition-particle-and-anti-mi-2-antibodies
#3
Richard Oluyinka Akintayo, Olanrewaju Festus Agbola, Abiodun Waliyullah Adeyemo, Olufemi Adelowo
Idiopathic inflammatory myopathies are a heterogeneous group of systemic diseases characterised by variable phenotypes of chronic progressive muscle weakness. Myositis-specific antibodies (MSAs) include antibodies to cytoplasmic signal recognition particle (SRP) and various tRNA synthetases as well as the nuclear helicase protein Mi-2. These antibodies are typically found only in a fraction of true myositis cases and they tend to be mutually exclusive. Few cases of coexistence of two MSAs in the same patient have been reported and these cases all involve an antisynthetase antibody coexisting with either anti-SRP or anti-Mi-2 antibody...
July 18, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28716624/mitochondrial-aminoacyl-trna-synthetases-in-human-disease
#4
REVIEW
Marie Sissler, Ligia Elena González-Serrano, Eric Westhof
Dysfunctions in mitochondria - the powerhouses of the cell - lead to several human pathologies. Because mitochondria integrate nuclear and mitochondrial genetic systems, they are richly intertwined with cellular activities. The nucleus-encoded mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs) are key components of the mitochondrial translation apparatus. Mutations in these enzymes predominantly affect the central nervous system (CNS) but also target other organs. Comparable mutations in mt-aaRSs can lead to vastly diverse diseases, occurring at different stages in life, and within different tissues; this represents a confounding issue...
July 14, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28716262/new-genetic-causes-for-complex-hereditary-spastic-paraplegia
#5
Paulo Victor Sgobbi de Souza, Thiago Bortholin, Renan Braido Dias, Marco Antônio Troccoli Chieia, Stênio Burlin, Fernando George Monteiro Naylor, Wladimir Bocca Vieira de Rezende Pinto, Acary Souza Bulle Oliveira
INTRODUCTION: Hereditary Spastic Paraplegia (HSP) represents a complex and heterogeneous group of rare neurodegenerative disorders that share a common clinical feature of weakness and lower limb spasticity that can occur alone or in combination with a constellation of other neurological or systemic signs and symptoms. Although the core clinical feature of weakness and lower limb spasticity is virtually universal, the genetic heterogeneity is almost uncountable with more than 70 genetic forms described so far...
August 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28679377/methionyl-trna-synthetase-overexpression-is-associated-with-poor-clinical-outcomes-in-non-small-cell-lung-cancer
#6
Eun Young Kim, Ji Ye Jung, Arum Kim, Kwangsoo Kim, Yoon Soo Chang
BACKGROUND: Methionyl-tRNA synthetase (MRS) plays a critical role in initiating translation by transferring Met to the initiator tRNA (tRNAi(Met)) and protection against ROS-mediated damage, suggesting that its overexpression is related to cancer growth and drug resistance. In this study, the clinical implication of MRS expression in non-small cell lung cancer (NSCLC) was evaluated. METHODS: Immunoblot and immunohistochemical (IHC) analyses were performed using tissue lysates and formalin-fixed paraffin embedded (FFPE) tissue blocks from wild type C57BL/6, LSL-Kras G12D, and LSL-Kras G12D:p53(fl/fl) mice...
July 5, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28679374/development-of-a-counterselectable-seamless-mutagenesis-system-in-lactic-acid-bacteria
#7
Yongping Xin, Tingting Guo, Yingli Mu, Jian Kong
BACKGROUND: Lactic acid bacteria (LAB) are receiving more attention to act as cell factories for the production of high-value metabolites. However, the molecular tools for genetic modifying these strains are mainly vector-based double-crossover strategies, which are laborious and inefficient. To address this problem, several counterselectable markers have been developed, while few of them could be used in the wild-type host cells without pretreatment. RESULTS: The pheS gene encoding phenylalanyl-tRNA synthetase alpha subunit was identified in Lactococcus lactis NZ9000 genome...
July 5, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28675565/compound-heterozygosity-for-loss-of-function-gars-variants-results-in-a-multisystem-developmental-syndrome-that-includes-severe-growth-retardation
#8
Stephanie N Oprescu, Xenia Chepa-Lotrea, Ryuichi Takase, Gretchen Golas, Thomas C Markello, David R Adams, Camilo Toro, Andrea L Gropman, Ya-Ming Hou, May Christine V Malicdan, William A Gahl, Cynthia J Tifft, Anthony Antonellis
Aminoacyl-tRNA synthetases (ARSs) are ubiquitously expressed enzymes that ligate amino acids onto tRNA molecules. Genes encoding ARSs have been implicated in myriad dominant and recessive disease phenotypes. Glycyl-tRNA synthetase (GARS) is a bifunctional ARS that charges tRNA(Gly) in the cytoplasm and mitochondria. GARS variants have been associated with dominant Charcot-Marie-Tooth disease but have not been convincingly implicated in recessive phenotypes. Here, we describe a patient from the NIH Undiagnosed Diseases Program with a multisystem, developmental phenotype...
July 4, 2017: Human Mutation
https://www.readbyqxmd.com/read/28660466/identity-elements-of-trna-as-derived-from-information-analysis
#9
Gabriel S Zamudio, Marco V José
The decipherment of the tRNA's operational code, known as the identity problem, requires the location of the sites in the tRNA structure that are involved in their correct recognition by the corresponding aminoacyl-tRNA synthetase. In this work, we determine the identity elements of each tRNA isoacceptor by means of the variation of information measure from information theory. We show that all isoacceptors exhibit sites associated with some bases of the anticodon. These sites form clusters that are scattered along the tRNA structure...
June 28, 2017: Origins of Life and Evolution of the Biosphere
https://www.readbyqxmd.com/read/28655838/nonredox-thiolation-in-trna-occurring-via-sulfur-activation-by-a-4fe-4s-cluster
#10
Simon Arragain, Ornella Bimai, Pierre Legrand, Sylvain Caillat, Jean-Luc Ravanat, Nadia Touati, Laurent Binet, Mohamed Atta, Marc Fontecave, Béatrice Golinelli-Pimpaneau
Sulfur is present in several nucleosides within tRNAs. In particular, thiolation of the universally conserved methyl-uridine at position 54 stabilizes tRNAs from thermophilic bacteria and hyperthermophilic archaea and is required for growth at high temperature. The simple nonredox substitution of the C2-uridine carbonyl oxygen by sulfur is catalyzed by tRNA thiouridine synthetases called TtuA. Spectroscopic, enzymatic, and structural studies indicate that TtuA carries a catalytically essential [4Fe-4S] cluster and requires ATP for activity...
June 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28655767/three-distinct-3-methylcytidine-m3c-methyltransferases-modify-trna-and-mrna-in-mice-and-humans
#11
Luang Xu, Xinyu Liu, Na Sheng, Kyaw Soe Oo, Junxin Liang, Yok Hian Chionh, Juan Xu, Fuzhou Ye, Yong-Gui Gao, Peter C Dedon, Xin-Yuan Fu
Chemical RNA modifications are central features of epitranscriptomics, highlighted by the discovery of modified ribonucleosides in mRNA and exemplified by the critical roles of RNA modifications in normal physiology and disease. Despite a resurgent interest in these modifications, the biochemistry of 3-methylcytidine (m3C) formation in mammalian RNAs is still poorly understood. However, the recent discovery of trm141 as the second gene responsible for m3C presence in RNA in fission yeast raises the possibility that multiple enzymes are involved in m3C formation in mammals as well...
June 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28650581/deficiency-of-wars2-encoding-mitochondrial-tryptophanyl-trna-synthetase-causes-severe-infantile-onset-leukoencephalopathy
#12
Benjamin E Theisen, Anastasia Rumyantseva, Julie S Cohen, Wendy A Alcaraz, Deepali N Shinde, Sha Tang, Siddarth Srivastava, Jonathan Pevsner, Aleksandra Trifunovic, Ali Fatemi
Pathogenic variants in the mitochondrial aminoacyl tRNA synthetases lead to deficiencies in mitochondrial protein synthesis and are associated with a broad range of clinical presentations usually with early onset and inherited in an autosomal recessive manner. Of the 19 mitochondrial aminoacyl tRNA synthetases, WARS2, encoding mitochondrial tryptophanyl tRNA synthetase, was as of late the only one that had not been associated with disease in humans. A case of a family with pathogenic variants in WARS2 that caused mainly intellectual disability, speech impairment, aggressiveness, and athetosis was recently reported...
June 26, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28650092/photoactivatable-mussel-based-underwater-adhesive-proteins-by-an-expanded-genetic-code
#13
Mathias Hauf, Florian Richter, Tobias Schneider, Thomas Faidt, Berta M Martins, Tobias Baumann, Patrick Durkin, Holger Dobbek, Karin Jacobs, Andreas Möglich, Nediljko Budisa
Marine mussels exhibit potent underwater adhesion abilities under hostile conditions employing 3,4-dihydroxy-phenylalanine (Dopa)-rich mussel-adhesive proteins (MAPs). However, their recombinant production is a major biotechnological challenge. Here, we have developed a novel strategy based on genetic code expansion by engineering efficient aminoacyl-tRNA synthetases (aaRSs) for the photocaged non-canonical amino acid (ncAA) ortho-nitrobenzyl Dopa (ONB-Dopa). The engineered ONB-DopaRS enables in vivo production of MAP type 5 site-specifically equipped with multiple instances of ONB-Dopa yielding spatiotemporally controlled underwater adhesives...
June 26, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28641210/comparative-analysis-of-polyspecificity-of-the-endogenous-trna-synthetase-of-different-expression-host-towards-photocrosslinking-amino-acids-using-an-in-silico-approach
#14
Nadarajan Saravanan Prabhu, Hyungdon Yun
Photo-induced covalent crosslinking has emerged as the powerful strategy for analyzing and characterizing the protein-protein interaction and mapping protein 3D conformations. In the last decades, a number of photocrosslinking amino acids have been reported but only a few have been efficiently utilized for photocrosslinking purposes. Recently, incorporation of diazirine containing photoactivatable analogs such as photo-methionine, photo-leucine, photo-isoleucine and photo-lysine into target proteins were accomplished in live cells (Human A549cells, HEK 293) by depleting corresponding natural amino acid and supplementing these analogs in the medium...
June 8, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28638448/ratio-of-autoantibodies-of-tumor-suppressor-aimp2-and-its-oncogenic-variant-is-associated-with-clinical-outcome-in-lung-cancer
#15
Ji Ye Jung, Eun Young Kim, Arum Kim, Joon Chang, Nam Hoon Kwon, Youngji Moon, Eun Joo Kang, Jun Sik Sung, Hyunbo Shim, Sunghoon Kim, Yoon Soo Chang
Aminoacyl-tRNA synthetase-interacting multi-functional protein 2 (AIMP2) works as potent tumor suppressor, while its splicing variant lacking exon 2 (AIMP2-DX2) competes with AIMP2 for binding to target proteins and compromises its anti-tumor activity. Assuming that AIMP2 and its variant AIMP2-DX2 could be released out to human sera in pathological condition, we investigated the diagnostic and prognostic usefulness of autoantibodies against AIMP2 and AIMP2-DX2 by measuring their serum levels in 80 normal and lung cancer samples that were matched in age, gender and smoking status...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28633377/emerging-mechanisms-of-aminoacyl-trna-synthetase-mutations-in-recessive-and-dominant-human-disease
#16
Rebecca Meyer-Schuman, Anthony Antonellis
Aminoacyl-tRNA synthetases (ARSs) are responsible for charging amino acids to cognate tRNA molecules, which is the essential first step of protein translation. Interestingly, mutations in genes encoding ARS enzymes have been implicated in a broad spectrum of human inherited diseases. Bi-allelic mutations in ARSs typically cause severe, early-onset, recessive diseases that affect a wide range of tissues. The vast majority of these mutations show loss-of-function effects and impair protein translation. However, it is not clear how a subset cause tissue-specific phenotypes...
June 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28632987/the-usher-syndrome-type-iiib-histidyl-trna-synthetase-mutation-confers-temperature-sensitivity
#17
Jamie A Abbott, Ethan Guth, Cindy Kim, Cathy Regan, Victoria M Siu, C Anthony Rupar, Borries Demeler, Christopher S Francklyn, Susan M Robey-Bond
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...
July 7, 2017: Biochemistry
https://www.readbyqxmd.com/read/28626001/krs-a-cut-away-from-release-in-exosomes
#18
Catherine Rabouille
Cancer cells often trigger an inflammatory process, which in some cases may be driven by the presence of lysyl-tRNA synthetase (KRS) in the medium. Kim et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201605118) now demonstrate that cleavage of the KRS by caspase-8 inside cells triggers its interaction with syntenin and its release in inflammatory exosomes.
July 3, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28625715/discovery-of-simplified-leucyladenylate-sulfamates-as-novel-leucyl-trna-synthetase-lrs-targeted-mammalian-target-of-rapamycin-complex-1-mtorc1-inhibitors
#19
Suyoung Yoon, Jong Hyun Kim, Yura Koh, Phuong-Thao Tran, Jihyae Ann, Ina Yoon, Jayun Jang, Won Kyung Kim, Sangkook Lee, Jiyoun Lee, Sunghoon Kim, Jeewoo Lee
Leucyl-tRNA synthetase (LRS) has been reported to be a possible mediator of intracellular amino acids signaling to mTORC1. Given that mTORC1 is associated with cell proliferation and tumorigenesis, the LRS-mediated mTORC1 pathway may offer an alternative strategy in anticancer therapy. In this study, we developed a series of simplified analogues of leucyladenylate sulfamate (1) as LRS-targeted mTORC1 inhibitors. We replaced the adenylate group with a N-(3,4-dimethoxybenzyl)benzenesulfonamide (2a) or a N-(2-phenoxyethyl)benzenesulfonamide groups (2b) that can maintain specific binding, but has more favorable physicochemical properties such as reduced polarity and asymmetric centers...
June 2, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28621923/capture-and-release-of-trna-by-the-t-loop-receptor-in-the-function-of-the-t-box-riboswitch
#20
Xianyang Fang, Malgorzata Michnicka, Yikan Zhang, Yun-Xing Wang, Edward P Nikonowicz
In Gram-positive bacteria, the tRNA-dependent T-box riboswitch system regulates expression of amino acid biosynthetic and aminoacyl-tRNA synthetase genes through a transcription attenuation mechanism. Binding of uncharged tRNA "closes" the switch, allowing transcription read-through. Structural studies of the 100-nucleotide stem I domain reveal tRNA utilizes base pairing and stacking interactions to bind the stem, but little is known structurally about the 180-nucleotide riboswitch core (stem I, stem III, and antiterminator stem) in complex with tRNA or the mechanism of coupling of the intermolecular binding domains crucial to T-box function...
July 18, 2017: Biochemistry
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