Read by QxMD icon Read

tRNA Synthetase

David S Lynch, Wei Jia Zhang, Rahul Lakshmanan, Justin A Kinsella, Günes Altiokka Uzun, Merih Karbay, Zeynep Tüfekçioglu, Hasmet Hanagasi, Georgina Burke, Nicola Foulds, Simon R Hammans, Anupam Bhattacharjee, Heather Wilson, Matthew Adams, Mark Walker, James A R Nicoll, Jeremy Chataway, Nick Fox, Indran Davagnanam, Rahul Phadke, Henry Houlden
Importance: Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a frequent cause of adult-onset leukodystrophy known to be caused by autosomal dominant mutations in the CSF1R (colony-stimulating factor 1) gene. The discovery that CSF1R mutations cause ALSP led to more accurate prognosis and genetic counseling for these patients in addition to increased interest in microglia as a target in neurodegeneration. However, it has been known since the discovery of the CSF1R gene that there are patients with typical clinical and radiologic evidence of ALSP who do not carry pathogenic CSF1R mutations...
October 17, 2016: JAMA Neurology
Young Ha Ahn, Sunyoung Park, Jeong June Choi, Bo-Kyung Park, Kyung Hee Rhee, Eunjoo Kang, Soyeon Ahn, Chul-Ho Lee, Jong Soo Lee, Kyung-Soo Inn, Mi-La Cho, Sung-Hwan Park, Kyunghee Park, Hae Jung Park, Jae Hyun Lee, Jung Won Park, Nam Hoon Kwon, Hyunbo Shim, Byung Woo Han, Pilhan Kim, Joo-Youn Lee, Youngho Jeon, Jin Won Huh, Mirim Jin, Sunghoon Kim
The N-terminal truncated form of a protein synthesis enzyme, tryptophanyl-tRNA synthetase (mini-WRS), is secreted as an angiostatic ligand. However, the secretion and function of the full-length WRS (FL-WRS) remain unknown. Here, we report that the FL-WRS, but not mini-WRS, is rapidly secreted upon pathogen infection to prime innate immunity. Blood levels of FL-WRS were increased in sepsis patients, but not in those with sterile inflammation. FL-WRS was secreted from monocytes and directly bound to macrophages via a toll-like receptor 4 (TLR4)-myeloid differentiation factor 2 (MD2) complex to induce phagocytosis and chemokine production...
October 17, 2016: Nature Microbiology
Chaoyang Zhou, Lingling Shi, Bin Ye, Haichao Feng, Ji Zhang, Ruifu Zhang, Xin Yan
Aside from applications in the production of commercial enzymes and metabolites, Bacillus amyloliquefaciens is also an important group of plant growth-promoting rhizobacteria that supports plant growth and suppresses phytopathogens. A host-genotype-independent counter-selectable marker would enable rapid genetic manipulation and metabolic engineering, accelerating the study of B. amyloliquefaciens and its development as both a microbial cell factory and plant growth-promoting rhizobacteria. Here, a host-genotype-independent counter-selectable marker pheS (*) was constructed through a point mutation of the gene pheS, which encodes the α-subunit of phenylalanyl-tRNA synthetase in Bacillus subtilis strain 168...
October 11, 2016: Applied Microbiology and Biotechnology
Abul Arif, Jie Jia, Dalia Halawani, Paul L Fox
Phosphorylation of many aminoacyl tRNA synthetases (AARSs) has been recognized for decades, but the contribution of post-translational modification to their primary role in tRNA charging and decryption of genetic code remains unclear. In contrast, phosphorylation is essential for performance of diverse noncanonical functions of AARSs unrelated to protein synthesis. Phosphorylation of glutamyl-prolyl tRNA synthetase (EPRS) has been investigated extensively in our laboratory for more than a decade, and has served as an archetype for studies of other AARSs...
October 8, 2016: Methods: a Companion to Methods in Enzymology
Sylvain Debard, Gaétan Bader, Johan-Owen De Craene, Ludovic Enkler, Séverine Bär, Daphné Laporte, Evelyne Myslinski, Bruno Senger, Sylvie Friant, Hubert Dominique Becker
By definition, cytosolic aminoacyl-tRNA synthetases (aaRSs) should be restricted to the cytosol of eukaryotic cells where they supply translating ribosomes with their aminoacyl-tRNA substrates. However, it has been shown that other translationally-active compartments like mitochondria and plastids can simultaneously contain the cytosolic aaRS and its corresponding organellar ortholog suggesting that both forms do not share the same organellar function. In addition, a fair number of cytosolic aaRSs have also been found in the nucleus of cells from several species...
October 7, 2016: Methods: a Companion to Methods in Enzymology
Mark D Vaughan, Zhengding Su, Elisabeth Daub, J F Honek
Bioincorporation of the methionine analogue S-(2-fluoroethyl)-l-homocysteine (l-MFE) into bacteriophage lysozyme overproduced in Escherichia coli results not only in the expected l-MFE incorporation but surprisingly substantial l-vinthionine incorporation into the labeled lysozymes. Synthetic l-vinthionine itself however is not activated by purified Escherichia coli methionyl-tRNA synthetase. The indirect preparation of vinthionine-containing proteins has the potential to be an alternate strategy to prepare vinyl thioether moieties for click chemistry applications on proteins...
September 26, 2016: Organic & Biomolecular Chemistry
Makito Hirano, Nobuyuki Oka, Akihiro Hashiguchi, Shuichi Ueno, Hikaru Sakamoto, Hiroshi Takashima, Yujiro Higuchi, Susumu Kusunoki, Yusaku Nakamura
Charcot-Marie-Tooth (CMT) disease is a complex of peripheral nervous system disorders. CMT type 2U (CMT2U) is an autosomal dominant disease caused by mutations in the MARS gene encoding methionyl-tRNA synthetase; this disease has thus been newly called AD-CMTax-MARS. A few families with mutations in the MARS gene have been reported, without detailed histopathological findings. We describe a 70-year-old woman who had bilateral dysesthesia of the soles since the age of 66 years. Sural nerve biopsy showed a decrease in the density of large myelinated nerve fibers...
October 7, 2016: Journal of the Peripheral Nervous System: JPNS
Shaileja Chopra, Andrés Palencia, Cornelia Virus, Sarah Schulwitz, Brenda R Temple, Stephen Cusack, John Reader
Antibiotic-producing microbes evolved self-resistance mechanisms to avoid suicide. The biocontrol Agrobacterium radiobacter K84 secretes the Trojan Horse antibiotic agrocin 84 that is selectively transported into the plant pathogen A. tumefaciens and processed into the toxin TM84. We previously showed that TM84 employs a unique tRNA-dependent mechanism to inhibit leucyl-tRNA synthetase (LeuRS), while the TM84-producer prevents self-poisoning by expressing a resistant LeuRS AgnB2. We now identify a mechanism by which the antibiotic-producing microbe resists its own toxin...
October 7, 2016: Nature Communications
Nevena Cvetesic, Ita Gruic-Sovulj
The covalent coupling of cognate amino acid-tRNA pairs by corresponding aminoacyl-tRNA synthetases (aaRS) defines the genetic code and provides aminoacylated tRNAs for ribosomal protein synthesis. Besides the cognate substrate, some non-cognate amino acids may also compete for tRNA aminoacylation. However, their participation in protein synthesis is generally prevented by an aaRS proofreading activity located in the synthetic site and in a separate editing domain. These mechanisms, coupled with the ability of certain aaRSs to discriminate well against non-cognate amino acids in the synthetic reaction alone, define the accuracy of the aminoacylation reaction...
October 3, 2016: Methods: a Companion to Methods in Enzymology
Tony D Davis, Poornima Mohandas, Maria I Chiriac, Glennon V Bythrow, Luis E N Quadri, Derek S Tan
Biosynthesis of bacterial natural-product virulence factors is emerging as a promising antibiotic target. Many such natural products are produced by nonribosomal peptide synthetases (NRPS) from amino acid precursors. To develop selective inhibitors of these pathways, we have previously described aminoacyl-AMS (sulfamoyladenosine) macrocycles that inhibit NRPS amino acid adenylation domains but not mechanistically-related aminoacyl-tRNA synthetases. To improve the cell permeability of these inhibitors, we explore herein replacement of the α-amino group with an α-hydroxy group...
September 16, 2016: Bioorganic & Medicinal Chemistry Letters
Sandra Chartrand, Jeffrey J Swigris, Lina Stanchev, Joyce S Lee, Kevin K Brown, Aryeh Fischer
OBJECTIVE: To describe the clinical phenotype and natural history of a cohort of patients with interstitial pneumonia with autoimmune features (IPAF). METHODS: A retrospective, single center study of 56 patients with IPAF evaluated between February 2008 and August 2014. All clinical data were extracted from the electronic medical record and longitudinal changes in forced vital capacity (FVC) were analyzed with mixed-effects, piecewise linear regression models that considered time as a continuous factor...
October 2016: Respiratory Medicine
Ala Abdelali, Maie Al-Bader, Narayana Kilarkaje
Diabetes induces oxidative stress, DNA damage and alters several intracellular signaling pathways in organ systems. This study investigated modulatory effects of Trans-Resveratrol on type 1 diabetes mellitus (T1DM)-induced abnormal spermatogenesis, DNA damage and alterations in poly (ADP-ribose) polymerase (PARP) signaling in rat testis. Trans-Resveratrol administration (5mg/kg/day, ip) to Streptozotocin-induced T1DM adult male Wistar rats from day 22-42 resulted in recovery of induced oxidative stress, abnormal spermatogenesis and inhibited DNA synthesis, and led to mitigation of 8-hydroxy-2'-deoxyguanosine formation in the testis and spermatozoa, and DNA double-strand breaks in the testis...
September 27, 2016: Toxicology and Applied Pharmacology
Tessa van Dijk, Fred van Ruissen, Bregje Jaeger, Richard J Rodenburg, Saskia Tamminga, Merel van Maarle, Frank Baas, Nicole I Wolf, Bwee Tien Poll-The
Mutations in the mitochondrial arginyl tRNA synthetase (RARS2) gene are associated with Pontocerebellar Hypoplasia type 6 (PCH6). Here we report two patients, compound heterozygous for RARS2 mutations, presenting with early onset epileptic encephalopathy and (progressive) atrophy of both supra- and infratentorial structures. Early pontocerebellar hypoplasia was virtually absent and respiratory chain (RC) defects could not be detected in muscle biopsies. Both patients carried a novel missense mutation c.1544A>G (p...
September 29, 2016: JIMD Reports
Michael H Schwartz, Jacob R Waldbauer, Lichun Zhang, Tao Pan
High translational fidelity is commonly considered a requirement for optimal cellular health and protein function. However, recent findings have shown that inducible mistranslation specifically with methionine engendered at the tRNA charging level occurs in mammalian cells, yeast and archaea, yet it was unknown whether bacteria were capable of mounting a similar response. Here, we demonstrate that Escherichia coli misacylates non-methionyl-tRNAs with methionine in response to anaerobiosis and antibiotic exposure via the methionyl-tRNA synthetase (MetRS)...
September 26, 2016: Nucleic Acids Research
Yi Shi, Na Wei, Xiang-Lei Yang
Aminoacyl tRNA synthetases (AARSs) are best known for their essential role in translation in the cytoplasm. The concept that AARSs also exist in the nucleus started to draw attention around the turn of the new millennium, when aminoacylated tRNAs were first found in the nuclei of Xenopus oocytes. It is now expected that all cytoplasmic AARSs are present in the nucleus. In addition to tRNA aminoacylation, nuclear AARSs were found to regulate a spectrum of biological processes and responses, with many AARSs functioning through regulation at the level of gene transcription...
September 21, 2016: Methods: a Companion to Methods in Enzymology
Ho Jeon Young, Jung Weon Lee, Sunghoon Kim
Aminoacyl-tRNA synthetases (ARSs) are essential enzymes that conjugate specific amino acids to their cognate tRNAs for protein synthesis. Besides their catalytic activity, recent studies have uncovered many additional functions of these enzymes through their interactions with diverse cellular factors. Among human ARSs, cytosolic lysyl-tRNA synthetase (KRS) is often highly expressed in cancer cells and tissues, and facilitates cancer cell migration and invasion through the interaction with the 67kDa laminin receptor on the plasma membrane...
September 20, 2016: Biochimica et Biophysica Acta
Sanga Mitra, Arpa Samadder, Pijush Das, Smarajit Das, Medhanjali Dasgupta, Jayprokas Chakrabarti
Screening large-scale ENCODE data of 625 cytoplasmic transfer RNA (tRNAs) and 37 aminoacyl tRNA synthetase (AARSs) human genes, we deconstruct the array of relations between 10 histone marks affecting 15 chromatin states; their tissue specificity and variations and interchange amongst normal, cancerous and stem cells. The histone marks of RNA Pol II transcribed AARS genes share, but also contrast with that on RNA Pol III transcribed tRNA genes. tRNAs with identical/similar sequences may be in significantly varying states even within the same cell line; the chromatin scaffold, where the tRNA gene resides, is the key determinant...
October 6, 2016: Journal of Biomolecular Structure & Dynamics
Viqar Showkat Banday, Kristina Lejon
Although Type 1 diabetes (T1D) is T cell mediated disease in the effector stage, the mechanism behind the initial β cell assault less understood. Metabolomic differences, including elevated levels of glutamic acid, have been observed in T1D patients prior to disease onset, as well as in pre-diabetic non-obese diabetic (NOD) mice. Increased levels of glutamic acid damage both neurons and beta cells, implying that this could contribute to the initial events of T1D pathogenesis. We investigated the underlying genetic factors and consequences of the increased levels of glutamic acid in NOD...
September 21, 2016: Immunology
Jordan W Monk, Sean P Leonard, Colin W Brown, Michael J Hammerling, Catherine Mortensen, Alejandro E Gutierrez, Nathan Y Shin, Ella Watkins, Dennis M Mishler, Jeffrey E Barrick
By introducing engineered tRNA and aminoacyl-tRNA synthetase pairs into an organism, its genetic code can be expanded to incorporate nonstandard amino acids (nsAAs). The performance of these orthogonal translation systems (OTSs) varies greatly, however, with respect to the efficiency and accuracy of decoding a reassigned codon as the nsAA. To enable rapid and systematic comparisons of these critical parameters, we developed a toolkit for characterizing any Escherichia coli OTS that reassigns the amber stop codon (TAG)...
September 20, 2016: ACS Synthetic Biology
Yiyan Wang, Meng-Lin Tsao
A new method has been developed to reassign the rare codon AGA in Escherichia coli by engineering an orthogonal tRNA/aminoacyl-tRNA synthetase pair derived from Methanocaldococcus jannaschii. The tRNA mutant was introduced with a UCU anticodon, and the synthetase was evolved to correctly recognize the modified tRNA anticodon loop and to selectively charge a target noncanonical amino acid (NAA) onto the tRNA. In order to maximize the efficiency of AGA codon reassignment, while avoiding the lethal effects caused by global codon reassignment in cellular proteins, an inducible promoter (araBAD) was utilized to provide temporal controls for overexpression of the aminoacyl-tRNA synthetase and switch on codon reassignment...
September 20, 2016: Chembiochem: a European Journal of Chemical Biology
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"