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tRNA Synthetase

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https://www.readbyqxmd.com/read/28103142/mapping-of-calf-death-in-japanese-black-cattle
#1
Takashi Hirano, Shota Nishimura, Hiromi Hara, Yoshikazu Sugimoto, Kei Hanzawa
Weak calf syndrome (WCS) is a major cause of calf death in Japanese Black cattle. Among IARS disorders, the isoleucyl-tRNA synthetase c.235G>C mutation has been identified as one of the causes of WCS. However, calf deaths differing from those attributed to IARS disorder has been occurring. To identify other genes potentially responsible for these calf deaths, we constructed three populations of three bulls (Bull-1, -2 and -3) that did not carry the IARS mutation, and dead calves (18, 28, and 31 calves) and healthy cattle (18, 15, and 10 cattle) sired by these bulls...
January 19, 2017: Animal Biotechnology
https://www.readbyqxmd.com/read/28095316/rewiring-protein-synthesis-from-natural-to-synthetic-amino-acids
#2
REVIEW
Yongqiang Fan, Christopher R Evans, Jiqiang Ling
BACKGROUND: The protein synthesis machinery uses 22 natural amino acids as building blocks that faithfully decode the genetic information. Such fidelity is controlled at multiple steps and can be compromised in nature and in the laboratory to rewire protein synthesis with natural and synthetic amino acids. SCOPE OF REVIEW: This review summarizes the major quality control mechanisms during protein synthesis, including aminoacyl-tRNA synthetases, elongation factors, and the ribosome...
January 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28095181/how-trnas-dictate-nuclear-codon-reassignments-only-a-few-can-capture-non-cognate-codons
#3
Martin Kollmar, Stefanie Mühlhausen
Messenger RNA decoding by tRNAs and tRNA charging by aminoacyl-tRNA synthetases are biochemically separated processes that nevertheless in general involve the same nucleotides. The combination of charging and decoding determines the genetic code. Codon reassignment happens when a differently charged tRNA replaces a former cognate tRNA. The recent discovery of the polyphyly of the yeast CUG sense codon reassignment challenged previous mechanistic considerations and led to the proposal of the so-called tRNA loss driven codon reassignment hypothesis...
January 17, 2017: RNA Biology
https://www.readbyqxmd.com/read/28089773/mitochondrial-diseases-yeast-as-a-model-for-the-study-of-suppressors
#4
Silvia Francisci, Arianna Montanari
Mitochondrial (mt) tRNA gene mutations are an important cause of human morbidity and are associated with different syndromes. We have previously shown that the mitochondrial protein synthesis elongation factor EF-Tu and isolated sequences from the carboxy-terminal domain of yeast and human mt leucyl-tRNA synthetases (LeuRS), have a wide range of suppression capability among different yeast mt tRNA mutants having defective respiratory phenotype. Here we show that the rescuing capability can be restricted to a specific sequence of six amino acids from the carboxy-terminal domain of mt LeuRS...
January 12, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28087278/prolyl-trna-synthetase-inhibition-promotes-cell-death-in-sk-mel-2%C3%A2-cells-through-gcn2-atf4-pathway-activation
#5
Takeo Arita, Megumi Morimoto, Yukiko Yamamoto, Hitoshi Miyashita, Satoshi Kitazawa, Takaharu Hirayama, Sou Sakamoto, Kazumasa Miyamoto, Ryutaro Adachi, Misa Iwatani, Takahito Hara
Protein translation is highly activated in cancer tissues through oncogenic mutations and amplifications, and this can support survival and aberrant proliferation. Therefore, blocking translation could be a promising way to block cancer progression. The process of charging a cognate amino acid to tRNA, a crucial step in protein synthesis, is mediated by tRNA synthetases such as prolyl tRNA synthetase (PRS). Interestingly, unlike pan-translation inhibitors, we demonstrated that a novel small molecule PRS inhibitor (T-3861174) induced cell death in several tumor cell lines including SK-MEL-2 without complete suppression of translation...
January 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28078567/the-c-abl-inhibitor-in-parkinson-disease
#6
REVIEW
Zhi-Hua Zhou, Yun-Fan Wu, Xue-Min Wang, Yong-Zhu Han
Parkinson's disease (PD) is an insidious onset neurodegenerative disease affecting approximately 1% of the population over the age of 65. So far available therapies for PD have only aimed at improving or alleviating symptoms, but not at slowing, preventing, and reversing the course of PD. Recently, some studies have indicated that the levels and activation of Abelson non-receptor tyrosine kinase (c-Abl, Abl1) were up-regulated in the brain tissue of patients with PD and demonstrated that c-Abl inhibitors could improve motor behavior, prevent the loss of dopamine neurons, inhibit phosphorylation of Cdk5, regulate α-synuclein phosphorylation and clearance, inhibit the tyrosine phosphorylation of parkin and decrease parkin substrate, for example, PARIS (zinc finger protein 746), AIMP2 (aminoacyl-tRNA synthetase-interacting multifunctional protein type2), FBP1 (fuse-binding protein 1), and synphilin-1...
January 11, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28077841/pars2-and-nars2-mutations-in-infantile-onset-neurodegenerative-disorder
#7
Takeshi Mizuguchi, Mitsuko Nakashima, Mitsuhiro Kato, Keitaro Yamada, Tohru Okanishi, Nina Ekhilevitch, Hanna Mandel, Ayelet Eran, Miyuki Toyono, Yukio Sawaishi, Hirotaka Motoi, Masaaki Shiina, Kazuhiro Ogata, Satoko Miyatake, Noriko Miyake, Hirotomo Saitsu, Naomichi Matsumoto
Here we present four unrelated families with six individuals that have infantile-onset developmental delay/regression and epilepsy. Whole-exome sequencing revealed compound heterozygous mutations, c.[283G>A];[607G>A] in a gene encoding prolyl-tRNA synthetase (PARS2) in one family. Two pairs of compound heterozygous mutations, c.[151C>T];[1184T>G] and c.[707T>G];[594+1G>A], and a homozygous mutation, c.[500A>G];[500A>G], in a gene encoding asparaginyl-tRNA synthetase (NARS2) were also identified in the other three families...
January 12, 2017: Journal of Human Genetics
https://www.readbyqxmd.com/read/28070678/trna-misacylation-with-methionine-in-the-mouse-gut-microbiome-in-situ
#8
Michael H Schwartz, Tao Pan
Global protein mistranslation with methionine has been shown to be a conserved biological process that affords distinct functional advantages in all three domains of life. In all instances, methionine mistranslation occurs through a regulated process where low-fidelity forms of methionyl-tRNA synthetase are conditionally induced to mischarge non-methionyl-tRNAs with methionine followed by the utilization of the misacylated tRNAs in translation. In mammals, methionine mistranslation contributes to oxidative stress response; in the hyperthermophilic archaeon Aeropyrum pernix, methionine mistranslation produces proteins that are better adapted to low temperature growth; in E...
January 9, 2017: Microbial Ecology
https://www.readbyqxmd.com/read/28069943/acetylation-promotes-tyrrs-nuclear-translocation-to-prevent-oxidative-damage
#9
Xuanye Cao, Chaoqun Li, Siyu Xiao, Yunlan Tang, Jing Huang, Shuan Zhao, Xueyu Li, Jixi Li, Ruilin Zhang, Wei Yu
Tyrosyl-tRNA synthetase (TyrRS) is well known for its essential aminoacylation function in protein synthesis. Recently, TyrRS has been shown to translocate to the nucleus and protect against DNA damage due to oxidative stress. However, the mechanism of TyrRS nuclear localization has not yet been determined. Herein, we report that TyrRS becomes highly acetylated in response to oxidative stress, which promotes nuclear translocation. Moreover, p300/CBP-associated factor (PCAF), an acetyltransferase, and sirtuin 1 (SIRT1), a NAD(+)-dependent deacetylase, regulate the nuclear localization of TyrRS in an acetylation-dependent manner...
January 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28043061/fars2-mutation-and-epilepsy-possible-link-with-early-onset-epileptic-encephalopathy
#10
Jae So Cho, Seung Hyo Kim, Ha Young Kim, Taesu Chung, Dongsup Kim, Sesong Jang, Seung Bok Lee, Seung Keun Yoo, Jongyeon Shin, Jong-Il Kim, Hunmin Kim, Hee Hwang, Jong-Hee Chae, Jieun Choi, Ki Joong Kim, Byung Chan Lim
Early-onset epileptic encephalopathy (EOEE) consists of a heterogeneous group of epilepsy phenotypes. Recent technological advances in molecular biology have also rapidly expanded the genotype of EOEE. Genes involved in diverse molecular pathways, including ion channels, synaptic structure, transcription regulation, and cellular growth, have been implicated in EOEE. Mitochondrial aminoacyl tRNA synthetase, which plays a key role in mitochondrial protein synthesis by attaching 20 different amino acids to the tRNA tail, has been recently linked with the epilepsy phenotype...
December 2, 2016: Epilepsy Research
https://www.readbyqxmd.com/read/28042700/a-versatile-approach-for-site-specific-lysine-acylation-in-proteins
#11
Zhipeng A Wang, Yadagiri Kurra, Xin Wang, Yu Zeng, Yan-Jiun Lee, Vangmayee Sharma, Hening Lin, Susie Y Dai, Wenshe R Liu
Using amber suppression in coordination with a mutant pyrrolysyl-tRNA synthetase-tRNA(Pyl) pair, azidonorleucine is genetically encoded in E. coli. Its genetic incorporation followed by traceless Staudinger ligation with a phosphinothioester allows the convenient synthesis of a protein with a site-specifically installed lysine acylation. By simply changing the phosphinothioester identity, any lysine acylation type could be introduced. Using this approach, we demonstrated that both lysine acetylation and lysine succinylation can be installed selectively in ubiquitin and synthesized histone H3 with succinylation at its K4 position (H3K4su)...
January 2, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28039312/sarcoplasmic-mxa-expression-a-valuable-marker-of-dermatomyositis
#12
Akinori Uruha, Atsuko Nishikawa, Rie S Tsuburaya, Kohei Hamanaka, Masataka Kuwana, Yurika Watanabe, Shigeaki Suzuki, Norihiro Suzuki, Ichizo Nishino
OBJECTIVE: To evaluate the diagnostic value of myxovirus resistance A (MxA) expression in the cytoplasm of myofibers in the diagnosis of dermatomyositis (DM). METHODS: We assessed the sensitivity and specificity of the sarcoplasmic expression of MxA in muscles with DM by immunohistochemistry in consecutive cases of DM (n = 34) and other idiopathic inflammatory myopathies (n = 120: 8 with polymyositis, 16 with anti-tRNA-synthetase antibody-associated myositis, 46 with immune-mediated necrotizing myopathy, and 50 with inclusion body myositis) and compared them with conventional pathologic hallmarks of DM, including perifascicular atrophy (PFA) and membrane attack complex (MAC) deposition on endomysial capillaries...
December 30, 2016: Neurology
https://www.readbyqxmd.com/read/28039138/an-effective-counterselection-system-for-listeria-monocytogenes-and-its-use-to-characterize-10403s-strain-monocin-genomic-region
#13
Tal Argov, Lev Rabinovich, Nadejda Sigal, Anat A Herskovits
Construction of Listeria monocytogenes mutants by allelic exchange has been laborious and time consuming due to lack of proficient selection markers for the final recombination event. That is, a marker conveying substance sensitivity to the bacteria bearing it, enabling the exclusion of merodiploids and selection for plasmid loss. In order to address this issue, we engineered a counterselection marker based on a mutated phenylalanyl-tRNA synthetase gene (pheS*). This mutation renders the phenylalanine-binding site of the enzyme more promiscuous and allows the binding of the toxic p-chloro-phenylalanine analog (p-Cl-phe) as a substrate...
December 30, 2016: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28006787/role-of-mir-215-in-hirschsprung-s-disease-pathogenesis-by-targeting-siglec-8
#14
Hao Lei, Hongxing Li, Hua Xie, Chunxia Du, Yankai Xia, Weibing Tang
BACKGROUND/AIMS: Hirschsprung's disease (HSCR), known as aganglionosis, is an infrequent congenital gut motility disorder characterized by absence of enteric neurons. In this study, we focus on the role of the intronic miR-215 and its host gene isoleucyl-tRNA synthetase 2 (IARS2) in the pathogenesis of HSCR. METHODS: Quantitative real time PCR and Western blot were used to detect the miRNA, mRNAs, and proteins levels. The dual-luciferase reporter gene assay confirmed the direct regulation of the specific mRNA and miRNAs in cell lines...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28003514/s-cerevisiae-trm140-has-two-recognition-modes-for-3-methylcytidine-modification-of-the-anticodon-loop-of-trna-substrates
#15
Lu Han, Erin Marcus, Sonia D'Silva, Eric M Phizicky
The 3-methylcytidine (m3C) modification is ubiquitous in eukaryotic tRNA, widely found at C32 in the anticodon loop of tRNAThr, tRNASer, and some tRNAArg species, as well as in the variable loop (V-loop) of certain tRNASer species. In the yeast Saccharomyces cerevisiae, formation of m3C32 requires Trm140 for six tRNA substrates, including three tRNAThr species and three tRNASer species, whereas in Schizosacchomyces pombe, two Trm140 homologs are employed, one for tRNAThr and one for tRNASer. The occurrence of a single Trm140 homolog is conserved broadly among Ascomycota, whereas multiple Trm140-related homologs are found in metazoans and other fungi...
December 21, 2016: RNA
https://www.readbyqxmd.com/read/27989759/a-new-set-of-assays-for-the-discovery-of-aminoacyl-trna-synthetase-inhibitors
#16
Adélaïde Saint-Léger, Lluís Ribas de Pouplana
Current biochemical methods available to monitor the activity of aminoacyl-tRNA synthetases (ARS) are ill-suited to high-throughput screening approaches for the identification of small-molecule inhibitors of these enzymes. In an attempt to improve the limitations of current assays we have developed a suite of new methods designed to streamline the discovery of new ARS antagonists. This set of assays includes approaches to monitor ARS activity in vitro, in human cells, and in bacteria. They are applicable to several ARSs from any given organism, can be easily adapted to very high-throughput set-ups, and allow for a multi-factorial selection of drug candidates...
January 15, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/27987323/translation-system-engineering-in-escherichia-coli-enhances-non-canonical-amino-acid-incorporation-into-proteins
#17
Rui Gan, Jessica G Perez, Erik D Carlson, Ioanna Ntai, Farren J Isaacs, Neil L Kelleher, Michael C Jewett
The ability to site-specifically incorporate noncanonical amino acids (ncAAs) into proteins has made possible the study of protein structure and function in fundamentally new ways, as well as the synthesis of unnatural polymers. However, the task of site-specifically incorporating multiple ncAAs into proteins with high purity and yield continues to present a challenge. At the heart of this challenge lies the lower efficiency of engineered orthogonal translation system components compared to their natural counterparts (e...
December 17, 2016: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/27981881/systematic-characterization-of-artificial-small-rna-mediated-inhibition-of-escherichia-coli-growth
#18
Emiko Noro, Masaru Mori, Gakuto Makino, Yuki Takai, Sumiko Ohnuma, Asako Sato, Masaru Tomita, Kenji Nakahigashi, Akio Kanai
A new screening system for artificial small RNAs (sRNAs) that inhibit the growth of Escherichia coli was constructed. In this system, we used a plasmid library to express RNAs of ∼120 nucleotides, each with a random 30-nucleotide sequence that can recognize its target mRNA(s). After approximately 60,000 independent colonies were screened, several plasmids that inhibited bacterial growth were isolated. To understand the inhibitory mechanism, we focused on one sRNA, S-20, that exerted a strong inhibitory effect...
December 16, 2016: RNA Biology
https://www.readbyqxmd.com/read/27977303/tyrosyl-trna-synthetase-inhibitors-a-patent-review
#19
Juan Sun, Peng-Cheng Lv, Hai-Liang Zhu
Bacterial infection has been a consistent and relentless threat to human health because of emerging resistance to existing antibiotics. Therefore, much of the research has been focused on the design of new potent antibacterial agents. Tyrosyl-tRNA synthetase (TyrRS), as a member of aminoacyl-tRNA synthetase family, could recognize the information including the coincident tRNA molecules and the amino acids' structures, which are essential in translating the coded information into protein structures in nucleic acids...
December 15, 2016: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/27966891/combining-sense-and-nonsense-codon-reassignment-for-site-selective-protein-modification-with-unnatural-amino-acids
#20
Zhenling Cui, Sergey Mureev, Mark E Polinkovsky, Zakir Tnimov, Zhong Guo, Thomas Durek, Alun Jones, Kirill Alexandrov
Incorporation of unnatural amino acids (uAAs) via codon reassignment is a powerful approach for introducing novel chemical and biological properties to synthesized polypeptides. However, the site-selective incorporation of multiple uAAs into polypeptides is hampered by the limited number of reassignable nonsense codons. This challenge is addressed in the current work by developing Escherichia coli in vitro translation system depleted of specific endogenous tRNAs. The translational activity in this system is dependent on the addition of synthetic tRNAs for the chosen sense codon...
December 30, 2016: ACS Synthetic Biology
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