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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/28716624/mitochondrial-aminoacyl-trna-synthetases-in-human-disease
#2
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
#3
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/28708455/functionality-of-trnas-encoded-in-a-mobile-genetic-element-from-an-acidophilic-bacterium
#4
Pamela Alamos, Mario Tello, Paula Bustamante, Fernanda Gutiérrez, Amir Shmaryahu, Juan Maldonado, Gloria Levicán, Omar Orellana
The genome of the acidophilic, bioleaching bacterium Acidithiobacillus ferrooxidans, strain ATCC 23270, contains 95 predicted tRNA genes. Thirty-six of these genes (all 20 species) are clustered within an actively excising integrative-conjugative element (ICEAfe1). We speculated that these tRNA genes might have a role in adapting the bacterial tRNA pool to the codon usage of ICEAfe1 genes. To answer this question, we carried out theoretical calculations of the global tRNA adaptation index to the entire A. ferrooxidans genome with and without the ICEAfe1 encoded tRNA genes...
July 14, 2017: RNA Biology
https://www.readbyqxmd.com/read/28698277/deep-sea-hydrothermal-vent-viruses-compensate-for-microbial-metabolism-in-virus-host-interactions
#5
Tianliang He, Hongyun Li, Xiaobo Zhang
Viruses are believed to be responsible for the mortality of host organisms. However, some recent investigations reveal that viruses may be essential for host survival. To date, it remains unclear whether viruses are beneficial or harmful to their hosts. To reveal the roles of viruses in the virus-host interactions, viromes and microbiomes of sediment samples from three deep-sea hydrothermal vents were explored in this study. To exclude the influence of exogenous DNAs on viromes, the virus particles were purified with nuclease (DNase I and RNase A) treatments and cesium chloride density gradient centrifugation...
July 11, 2017: MBio
https://www.readbyqxmd.com/read/28688370/whole-transcriptome-rnaseq-analysis-of-oenococcus-oeni-reveals-distinct-intra-specific-expression-patterns-during-malolactic-fermentation-including-genes-involved-in-diacetyl-metabolism
#6
Peter R Sternes, Peter J Costello, Paul J Chambers, Eveline J Bartowsky, Anthony R Borneman
We report the first whole transcriptome RNAseq analysis of the wine-associated lactic acid bacterium Oenococcus oeni using a combination of reference-based mapping and de novo transcript assembly in three distinct strains during malolactic fermentation in Cabernet Sauvignon wine. Two of the strains (AWRIB551 and AWRIB552) exhibited similar transcriptomes relative to the third strain (AWRIB419) which was dissimilar by comparison. Significant intra-specific variation for genes related to glycolysis/gluconeogenesis, purine metabolism, aminoacyl-tRNA biosynthesis, ABC transporters and phosphotransferase systems was observed...
June 28, 2017: International Journal of Food Microbiology
https://www.readbyqxmd.com/read/28679533/a-hypertension-associated-mitochondrial-dna-mutation-alters-the-tertiary-interaction-and-function-of-trnaleu-uur
#7
Mi Zhou, Meng Wang, Ling Xue, Zhi Lin, Qiufen He, Wenwen Shi, Yaru Chen, Xiaofen Jin, Haiying Li, Pingping Jiang, Min-Xin Guan
Several mitochondrial tRNA mutations have been associated with hypertension, but their pathophysiology remains poorly understood. In this report, we identified a novel homoplasmic 3253T>C mutation in the mitochondrial tRNALeu(UUR) gene in a Han Chinese family with maternally inherited hypertension. The m.3253T>C mutation affected a highly conserved uridine at position 22 at the D-stem of tRNALeu(UUR), introducing a G-C base pairing (G13-C22) at the D-stem and a tertiary base pairing (C22-G46) between the D-stem and the variable loop...
July 5, 2017: Journal of Biological Chemistry
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/28650581/deficiency-of-wars2-encoding-mitochondrial-tryptophanyl-trna-synthetase-causes-severe-infantile-onset-leukoencephalopathy
#10
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
#11
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/28638448/ratio-of-autoantibodies-of-tumor-suppressor-aimp2-and-its-oncogenic-variant-is-associated-with-clinical-outcome-in-lung-cancer
#12
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
#13
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
#14
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/28621923/capture-and-release-of-trna-by-the-t-loop-receptor-in-the-function-of-the-t-box-riboswitch
#15
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
https://www.readbyqxmd.com/read/28616572/reversible-lysine-acetylation-regulates-nuclear-translocation-of-tyrrs-to-counteract-genotoxic-oxidative-stress
#16
Chaoqun Li, Wei Yu
Aminoacyl-tRNA synthetases, catalyzing the first step of protein synthesis, have been shown to involve with multiple additional physiologic responses. Here, we summarize our findings that p300/CBP-Associated Factor and Sirtuin 1 play the reversible acetylation role in regulating the nuclear translocation of Tyrosyl-tRNA synthetase and activating transcription factor E2F1, thus facilitating the repair of damaged DNA.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28611052/caspase-8-controls-the-secretion-of-inflammatory-lysyl-trna-synthetase-in-exosomes-from-cancer-cells
#17
Sang Bum Kim, Hye Rim Kim, Min Chul Park, Seongmin Cho, Peter C Goughnour, Daeyoung Han, Ina Yoon, YounHa Kim, Taehee Kang, Eunjoo Song, Pilhan Kim, Hyosun Choi, Ji Young Mun, Chihong Song, Sangmin Lee, Hyun Suk Jung, Sunghoon Kim
Aminoacyl-tRNA synthetases (ARSs), enzymes that normally control protein synthesis, can be secreted and have different activities in the extracellular space, but the mechanism of their secretion is not understood. This study describes the secretion route of the ARS lysyl-tRNA synthetase (KRS) and how this process is regulated by caspase activity, which has been implicated in the unconventional secretion of other proteins. We show that KRS is secreted from colorectal carcinoma cells within the lumen of exosomes that can trigger an inflammatory response...
July 3, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28608363/misynpat-an-integrated-knowledge-base-linking-clinical-genetic-and-structural-data-for-disease-causing-mutations-in-human-mitochondrial-aminoacyl-trna-synthetases
#18
Luc Moulinier, Raymond Ripp, Gaston Castillo, Olivier Poch, Marie Sissler
Numerous mutations in each of the mitochondrial aminoacyl-tRNA synthetases have been implicated in human diseases. The mutations are autosomal and recessive and lead mainly to neurological disorders, although with pleiotropic effects. The processes and interactions that drive the etiology of the disorders associated with mitochondrial aminoacyl-tRNA synthetases are far from understood. The complexity of the clinical, genetic and structural data requires concerted, interdisciplinary efforts to understand the molecular biology of these disorders...
June 12, 2017: Human Mutation
https://www.readbyqxmd.com/read/28604693/genetically-encoding-phosphotyrosine-and-its-nonhydrolyzable-analog-in-bacteria
#19
Xiaozhou Luo, Guangsen Fu, Rongsheng E Wang, Xueyong Zhu, Claudio Zambaldo, Renhe Liu, Tao Liu, Xiaoxuan Lyu, Jintang Du, Weimin Xuan, Anzhi Yao, Sean A Reed, Mingchao Kang, Yuhan Zhang, Hui Guo, Chunhui Huang, Peng-Yu Yang, Ian A Wilson, Peter G Schultz, Feng Wang
Tyrosine phosphorylation is a common protein post-translational modification that plays a critical role in signal transduction and the regulation of many cellular processes. Using a propeptide strategy to increase cellular uptake of O-phosphotyrosine (pTyr) and its nonhydrolyzable analog 4-phosphomethyl-L-phenylalanine (Pmp), we identified an orthogonal aminoacyl-tRNA synthetase-tRNA pair that allows site-specific incorporation of both pTyr and Pmp into recombinant proteins in response to the amber stop codon in Escherichia coli in good yields...
June 12, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28592109/roles-of-the-active-site-zn-ii-and-residues-in-substrate-discrimination-by-threonyl-trna-synthetase-an-md-and-qm-mm-investigation
#20
Mohamed M Aboelnga, James W Gauld
Threonyl-tRNA synthetase (ThrRS) is a Zn(II) containing enzyme that catalyzes the activation of threonine and its subsequent transfer to the cognate tRNA. This process is accomplished with remarkable fidelity, with ThrRS being able to discriminate its cognate substrate from similar analogues such as serine and valine. Molecular dynamics (MD) simulations and hybrid quantum mechanics/molecular mechanics (QM/MM) methods have been used to elucidate the role of Zn(II) in the aminoacylation mechanism of ThrRS. More specifically, the role of Zn(II) and active site residues in ThrRS's ability to discriminate between its cognate substrate l-threonine and the noncognate l-serine, l-valine, and d-threonine has been examined...
June 19, 2017: Journal of Physical Chemistry. B
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