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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
#1
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
#2
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
#3
Jamie A Abbott, Ethan Guth, Cindy Kim, Cathy Regan, Victoria M Siu, Charles 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 an 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...
June 20, 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
#4
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. Structure studies of the 100 nt stem I domain reveal tRNA utilizes base pairing and stacking interactions to bind the stem, but little is known structurally about the 180 nt riboswitch core (stem I, stem III, and antiterminator stem) in complex with tRNA and the mechanism of coupling of the intermolecular binding domains crucial to T-box function...
June 16, 2017: Biochemistry
https://www.readbyqxmd.com/read/28616572/reversible-lysine-acetylation-regulates-nuclear-translocation-of-tyrrs-to-counteract-genotoxic-oxidative-stress
#5
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
#6
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...
June 13, 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
#7
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
#8
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/the-roles-of-the-active-site-zn-ii-and-residues-in-substrate-discrimination-by-threonyl-trna-synthetase-an-md-and-qm-mm-investigation
#9
Mohamed M Aboelnga, James Wilson 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 analogs 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 non-cognate L-serine, L-valine and D-threonine has been examined...
June 7, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28588135/spatial-distribution-and-ribosome-binding-dynamics-of-ef-p-in-live-escherichia%C3%A2-coli
#10
Sonisilpa Mohapatra, Heejun Choi, Xueliang Ge, Suparna Sanyal, James C Weisshaar
In vitro assays find that ribosomes form peptide bonds to proline (Pro) residues more slowly than to other residues. Ribosome profiling shows that stalling at Pro-Pro-X triplets is especially severe but is largely alleviated in Escherichia coli by the action of elongation factor EF-P. EF-P and its eukaryotic/archaeal homolog IF5A enhance the peptidyl transfer step of elongation. Here, a superresolution fluorescence localization and tracking study of EF-P-mEos2 in live E. coli provides the first in vivo information about the spatial distribution and on-off binding kinetics of EF-P...
June 6, 2017: MBio
https://www.readbyqxmd.com/read/28586844/skeletal-muscle-involvement-in-antisynthetase-syndrome
#11
Eri Noguchi, Akinori Uruha, Shigeaki Suzuki, Kohei Hamanaka, Yuko Ohnuki, Jun Tsugawa, Yurika Watanabe, Jin Nakahara, Takashi Shiina, Norihiro Suzuki, Ichizo Nishino
Importance: Antisynthetase syndrome, characterized by myositis, interstitial lung disease, skin rash, arthropathy, and Raynaud phenomenon, is a clinical entity based on the presence of aminoacyl transfer RNA synthetase (ARS) antibodies in patients' serum. However, antisynthetase syndrome is not included in the histological subsets of idiopathic inflammatory myopathies. Objective: To elucidate the clinical features of myositis in patients with antisynthetase syndrome...
June 5, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28586482/determination-of-trna-aminoacylation-levels-by-high-throughput-sequencing
#12
Molly E Evans, Wesley C Clark, Guanqun Zheng, Tao Pan
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...
June 6, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28576863/evolving-mistranslating-trnas-through-a-phenotypically-ambivalent-intermediate-in-saccharomyces-cerevisiae
#13
Matthew D Berg, Kyle S Hoffman, Julie Genereaux, Safee Mian, Ryan S Trussler, David B Haniford, Patrick O'Donoghue, Christopher J Brandl
The genetic code converts information from nucleic acid into protein. The genetic code was thought to be immutable, yet many examples in nature indicate that variations to the code provide a selective advantage. We used a sensitive selection system involving suppression of a deleterious allele (tti2-L187P) in Saccharomyces cerevisiae to detect mistranslation and identify mechanisms that allow genetic code evolution. Though tRNA(Ser) containing a proline anticodon (UGG) is toxic, using our selection system, we identified four tRNA(Ser)UGG variants, each with a single mutation, that mistranslate at a tolerable level...
June 2, 2017: Genetics
https://www.readbyqxmd.com/read/28576772/incompatibility-between-mitochondrial-and-nuclear-genomes-during-oogenesis-results-in-ovarian-failure-and-embryonic-lethality
#14
Chunyang Zhang, Kristi L Montooth, Brian R Calvi
Mitochondrial dysfunction can cause female infertility. An important remaining question is the extent to which incompatibility between mitochondrial and nuclear genomes contributes to female infertility. It was previously shown that a mitochondrial haplotype from D. simulans (simw(501) ) is incompatible with a nuclear genome from the D. melanogaster strain Oregon-R (OreR), resulting in impaired development, which was enhanced at higher temperature. This mito-nuclear incompatibility is between alleles of the nuclear-encoded mitochondrial tyrosyl- tRNA synthetase (Aatm) and the mitochondrial-encoded tyrosyl-tRNA that it aminoacylates...
June 2, 2017: Development
https://www.readbyqxmd.com/read/28575390/self-protective-responses-to-norvaline-induced-stress-in-a-leucyl-trna-synthetase-editing-deficient-yeast-strain
#15
Quan-Quan Ji, Zhi-Peng Fang, Qing Ye, Cheng-Wu Chi, En-Duo Wang
The editing function of aminoacyl-tRNA synthetases (aaRSs) is indispensible for formation of the correct aminoacyl-tRNAs. Editing deficiency may lead to growth inhibition and the pathogenesis of various diseases. Herein, we confirmed that norvaline (Nva) but not isoleucine or valine is the major threat to the editing function of Saccharomyces cerevisiae leucyl-tRNA synthetase (ScLeuRS), both in vitro and in vivo. Nva could be misincorporated into the proteome of the LeuRS editing-deficient yeast strain (D419A/ScΔleuS), potentially resulting in dysfunctional protein folding and growth delay...
May 27, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28575328/identification-of-the-amino-acids-inserted-during-suppression-of-cftr-nonsense-mutations-and-determination-of-their-functional-consequences
#16
Xiaojiao Xue, Venkateshwar Mutyam, Amita Thakerar, James Mobley, Robert J Bridges, Steven M Rowe, Kim M Keeling, David M Bedwell
In-frame premature termination codons (PTCs) account for ∼11% of all disease-associated mutations. PTC suppression therapy utilizes small molecules that suppress translation termination at a PTC to restore synthesis of a full-length protein. PTC suppression is mediated by the base pairing of a near-cognate aminoacyl-tRNA with a PTC and subsequently, the amino acid becomes incorporated into the nascent polypeptide at the site of the PTC. However, little is known about the identity of the amino acid(s) inserted at a PTC during this process in mammalian cells, or how the surrounding sequence context influences amino acid incorporation...
May 31, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28575061/dissecting-structures-and-functions-of-seca-only-protein-conducting-channels-atpase-pore-structure-ion-channel-activity-protein-translocation-and-interaction-with-secyeg-secdf%C3%A2-yajc
#17
Ying-Hsin Hsieh, Ying-Ju Huang, Hao Zhang, Qian Liu, Yang Lu, Hsiuchin Yang, John Houghton, Chun Jiang, Sen-Fang Sui, Phang C Tai
SecA is an essential protein in the major bacterial Sec-dependent translocation pathways. E. coli SecA has 901 aminoacyl residues which form multi-functional domains that interact with various ligands to impart function. In this study, we constructed and purified tethered C-terminal deletion fragments of SecA to determine the requirements for N-terminal domains interacting with lipids to provide ATPase activity, pore structure, ion channel activity, protein translocation and interactions with SecYEG-SecDF•YajC...
2017: PloS One
https://www.readbyqxmd.com/read/28566605/dermatomyositis-with-rapidly-progressive-interstitial-lung-disease-treated-with-rituximab-a-report-of-3-cases-in-japan
#18
Kenichiro Tokunaga, Noboru Hagino
We performed a retrospective chart review of three patients with hypomyopathic dermatomyositis and rapidly progressive interstitial lung disease. The patients were Japanese women of 71, 69, and 65 years of age. Two patients were anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive and 1 was anti-aminoacyl-tRNA synthetase (anti-ARS) antibody-positive. Their respiratory statuses deteriorated despite the administration of glucocorticoid, calcineurin inhibitors, and intravenous cyclophosphamide therapy...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28559487/a-toxin-involved-in-salmonella-persistence-regulates-its-activity-by-acetylating-its-cognate-antitoxin-a-modification-reversed-by-cobb-sirtuin-deacetylase
#19
Chelsey M VanDrisse, Anastacia R Parks, Jorge C Escalante-Semerena
Bacterial toxin-antitoxin systems trigger the onset of a persister state by inhibiting essential cellular processes. The TacT toxin of Salmonella enterica is known to induce a persister state in macrophages through the acetylation of aminoacyl-tRNAs. Here, we show that the TacT toxin and the TacA antitoxin work as a complex that modulates TacT activity via the acetylation state of TacA. TacT acetylates TacA at residue K44, a modification that is removed by the NAD(+)-dependent CobB sirtuin deacetylase. TacA acetylation increases the activity of TacT, downregulating protein synthesis...
May 30, 2017: MBio
https://www.readbyqxmd.com/read/28558053/novel-mrna-specific-effects-of-ribosome-drop-off-on-translation-rate-and-polysome-profile
#20
Pierre Bonnin, Norbert Kern, Neil T Young, Ian Stansfield, M Carmen Romano
The well established phenomenon of ribosome drop-off plays crucial roles in translational accuracy and nutrient starvation responses during protein translation. When cells are under stress conditions, such as amino acid starvation or aminoacyl-tRNA depletion due to a high level of recombinant protein expression, ribosome drop-off can substantially affect the efficiency of protein expression. Here we introduce a mathematical model that describes the effects of ribosome drop-off on the ribosome density along the mRNA and on the concomitant protein synthesis rate...
May 2017: PLoS Computational Biology
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