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JOURNAL ARTICLE
Suzuka Matsuoka, Keiichi Fujiwara, Yuki Takigawa, Saki Ito, Sho Mitsumune, Keisuke Shiraha, Mayu Goda, Tomoyoshi Inoue, Miho Fujiwara, Eri Nakamura, Hiromi Watanabe, Kenichiro Kudo, Akiko Sato, Ken Sato, Takuo Shibayama
A 70-year-old woman with anti-aminoacyl-tRNA synthetase (ARS) antibody-positive interstitial lung disease (ARS-ILD) received daily medications and regular cyclophosphamide cycles for recurring exacerbations. Approximately four years after immunosuppression initiation, the patient was admitted for progressive dyspnea on exertion. Chest computed tomography (CT) findings were suggestive of acute exacerbation. Despite intensified immunosuppressive treatment, the radiographic findings worsened, and serum Krebs von den Lungen-6 (KL-6) levels increased...
March 25, 2024: Internal Medicine
#22
REVIEW
YouJin Kim, Suho Cho, Joo-Chan Kim, Hee-Sung Park
The advancement of genetic code expansion (GCE) technology is attributed to the establishment of specific aminoacyl-tRNA synthetase/tRNA pairs. While earlier improvements mainly focused on aminoacyl-tRNA synthetases, recent studies have highlighted the importance of optimizing tRNA sequences to enhance both unnatural amino acid incorporation efficiency and orthogonality. Given the crucial role of tRNAs in the translation process and their substantial impact on overall GCE efficiency, ongoing efforts are dedicated to the development of tRNA engineering techniques...
2024: Frontiers in Genetics
#23
JOURNAL ARTICLE
Junyi Ju, Hui Zhang, Moubin Lin, Zifeng Yan, Liwei An, Zhifa Cao, Dandan Geng, Jingwu Yue, Yang Tang, Luyang Tian, Fan Chen, Yi Han, Wenjia Wang, Shimin Zhao, Jiao Shi, Zhaocai Zhou
Lactylation has been recently identified as a new type of posttranslational modification widely occurring on lysine residues of both histone and non-histone proteins. The acetyl transferase p300 is thought to mediate protein lactylation, yet the cellular concentration of the proposed lactyl-donor, lactyl-coenzyme A is about 1,000 times lower than that of acetyl-CoA, raising the question whether p300 is a genuine lactyl-transferase. Here, we report the Alanyl-tRNA synthetase 1 (AARS1) moonlights as a bona fide lactyl-transferase that directly uses lactate and ATP to catalyze protein lactylation...
March 21, 2024: Journal of Clinical Investigation
#24
Manuel Castro de Moura, Francesc Miro, Jung Min Han, Sunghoon Kim, Antonio Celada, Lluís Ribas de Pouplana
[This corrects the article DOI: 10.1371/journal.pntd.0001398.].
March 2024: PLoS Neglected Tropical Diseases
#25
JOURNAL ARTICLE
Danique Beijer, Sheila Marte, Jiaxin C Li, Willem De Ridder, Jessie Z Chen, Abigail L D Tadenev, Kathy E Miers, Tine Deconinck, Richard Macdonell, Wilson Marques, Peter De Jonghe, Samia L Pratt, Rebecca Meyer-Schuman, Stephan Züchner, Anthony Antonellis, Robert W Burgess, Jonathan Baets
Pathogenic variants in six aminoacyl-tRNA synthetase (ARS) genes are implicated in neurological disorders, most notably inherited peripheral neuropathies. ARSs are enzymes that charge tRNA molecules with cognate amino acids. Pathogenic variants in asparaginyl-tRNA synthetase ( NARS1 ) cause a neurological phenotype combining developmental delay, ataxia and demyelinating peripheral neuropathy. NARS1 has not yet been linked to axonal Charcot-Marie-Tooth disease. Exome sequencing of patients with inherited peripheral neuropathies revealed three previously unreported heterozygous NARS1 variants in three families...
2024: Brain communications
#26
JOURNAL ARTICLE
Nishi Gandha Gogoi, Aziza Rahman, Pankaj Dutta, Jiban Saikia, Anupaul Baruah, Jyotirekha G Handique
Curcumin conjugated heterocyclic compounds are potent candidates with drug likeness against various bacterial pathogens. A set of curcumin-based pyrrole conjugates (CPs) were synthesized and characterized by FT-IR, 1H and 13C NMR and HR-MS techniques. The results free radical scavenging activity of the synthesized CPs, evaluated by FRAP and CUPRAC assays, showed the potency of these compounds as effective antioxidants. CP3 exhibits the highest antioxidant activity amongst the CPs. The bactericidal efficacy of CPs was screened against ESKAP bacterial pathogens, and CPs were found to possess better antibacterial property than curcumin, specifically against staphylococcus aureus bacteria...
March 15, 2024: Chemistry & Biodiversity
#27
JOURNAL ARTICLE
Tsuneo Sasai, Yuki Ishikawa, Ran Nakashima, Takuya Isayama, Kiminobu Tanizawa, Tomohiro Handa, Mirei Shirakashi, Ryosuke Hiwa, Hideaki Tsuji, Koji Kitagori, Shuji Akizuki, Hajime Yoshifuji, Tsuneyo Mimori, Akio Morinobu
Anti-aminoacyl-tRNA synthetase (ARS) antibodies are myositis-specific antibodies associated with anti-synthetase syndrome (ASSD). Some patients are positive for anti-ARS antibodies on enzyme-linked immunosorbent assay (ELISA) but negative on RNA-immunoprecipitation (RNA-IP) (the gold standard method). Whether these patients should be considered truly positive for anti-ARS antibodies remains unclear. Therefore, we investigated the clinical characteristics of these patients and verified the authenticity of their anti-ARS positivity...
March 15, 2024: Immunological Medicine
#28
MULTICENTER STUDY
Aravinthan Loganathan, Giovanni Zanframundo, Akira Yoshida, Sara Faghihi-Kashani, Iazsmin Bauer Ventura, Eduardo Dourado, Francisca Bozan, Gianluca Sambataro, Yasuhiko Yamano, Sharon Sangmee Bae, Darosa Lim, Angela Ceribelli, Natasa Isailovic, Carlo Selmi, Noreen Fertig, Elena Bravi, Yuko Kaneko, André Pinto Saraiva, Vega Jovani, Javier Bachiller-Corral, Jose Cifrian, Antonio Mera-Varela, Siamak Moghadam-Kia, Veronica Wolff, Julien Campagne, Alain Meyer, Margherita Giannini, Konstantinos Triantafyllias, Johannes Knitza, Latika Gupta, Yair Molad, Florenzo Iannone, Ilaria Cavazzana, Matteo Piga, Giacomo De Luca, Sarah Tansley, Emanuele Bozzalla-Cassione, Francesco Bonella, Tamera J Corte, Tracy J Doyle, David Fiorentino, Miguel Angel Gonzalez-Gay, Marie Hudson, Masataka Kuwana, Ingrid E Lundberg, Andrew L Mammen, Neil John McHugh, Fredrick W Miller, Carlomaurizio Montecucco, Chester V Oddis, Jorge Rojas-Serrano, Jens Schmidt, Carlo Alberto Scirè, Albert Selva-O'Callaghan, Victoria P Werth, Claudia Alpini, Sara Bozzini, Lorenzo Cavagna, Rohit Aggarwal
OBJECTIVES: The CLASS (Classification Criteria of Anti-Synthetase Syndrome) project is a large international multicentre study that aims to create the first data-driven anti-synthetase syndrome (ASSD) classification criteria. Identifying anti-aminoacyl tRNA synthetase antibodies (anti-ARS) is crucial for diagnosis, and several commercial immunoassays are now available for this purpose. However, using these assays risks yielding false-positive or false-negative results, potentially leading to misdiagnosis...
February 2024: Clinical and Experimental Rheumatology
#29
JOURNAL ARTICLE
Yusuke Kato, Hirotada Mori
Genetic instability of synthetic genetic devices is a key obstacle for practical use. This problem is particularly critical in kill-switches for conditional host killing. Here, we propose a genetically stable kill-switch based on a "demon and angel" expression construct of a toxic essential gene. The kill-switch conditionally overexpresses the toxic essential gene. Additionally, the identical essential gene is deleted in the genome. The essential gene is expressed at a low level to maintain host survival in the OFF state and kills the host by the overexpression in the ON state...
2024: Frontiers in Bioengineering and Biotechnology
#30
JOURNAL ARTICLE
Pallob Barai, Jie Chen
Aminoacyl-tRNA synthetases (AARSs) play an indispensable role in the translation of mRNAs into proteins. It has become amply clear that AARSs also have non-canonical or non-translational, yet essential, functions in a myriad of cellular and developmental processes. In this mini-review we discuss the current understanding of the roles of threonyl-tRNA synthetase (TARS) beyond protein synthesis and the underlying mechanisms. The two proteins in eukaryotes - cytoplasmic TARS1 and mitochondrial TARS2 - exert their non-canonical functions in the regulation of gene expression, cell signaling, angiogenesis, inflammatory responses, and tumorigenesis...
March 13, 2024: Biochemical Society Transactions
#31
JOURNAL ARTICLE
Wei Lu, Naohiro Terasaka, Yuriko Sakaguchi, Takeo Suzuki, Tsutomu Suzuki, Hiroaki Suga
In the hypothetical RNA world, ribozymes could have acted as modern aminoacyl-tRNA synthetases (ARSs) to charge tRNAs, thus giving rise to the peptide synthesis along with the evolution of a primitive translation apparatus. We previously reported a T-boxzyme, Tx2.1, which selectively charges initiator tRNA with N-biotinyl-phenylalanine (BioPhe) in situ in a Flexible In-vitro Translation (FIT) system to produce BioPhe-initiating peptides. Here, we performed in vitro selection of elongation-capable T-boxzymes (elT-boxzymes), using para-azido-l-phenylalanine (PheAZ) as an acyl-donor...
March 13, 2024: Nucleic Acids Research
#32
Amanda Gerard, Elizabeth Mizerik, Carrie A Mohila, Sarah AlAwami, Jill V Hunter, Debra L Kearney, Seema R Lalani, Fernando Scaglia
PARS2 encodes an aminoacyl-tRNA synthetase that catalyzes the ligation of proline to mitochondrial prolyl-tRNA molecules. Diseases associated with PARS2 primarily affect the central nervous system, causing early infantile developmental epileptic encephalopathies (EIDEE; DEE75; MIM #618437) with infantile-onset neurodegeneration. Dilated cardiomyopathy has also been reported in the affected individuals. About 10 individuals to date have been described with pathogenic biallelic variants in PARS2. While many of the reported individuals succumbed to the disease in the first two decades of life, autopsy findings have not yet been reported...
March 12, 2024: American Journal of Medical Genetics. Part A
#33
JOURNAL ARTICLE
Tianyu Gao, Jiantao Guo, Wei Niu
Emerging microorganism Pseudomonas putida KT2440 is utilized for the synthesis of biobased chemicals from renewable feedstocks and for bioremediation. However, the methods for analyzing, engineering, and regulating the biosynthetic enzymes and protein complexes in this organism remain underdeveloped.Such attempts can be advanced by the genetic code expansion-enabled incorporation of noncanonical amino acids (ncAAs) into proteins, which also enables further controls over the strain's biological processes. Here, we give a step-by-step account of the incorporation of two ncAAs into any protein of interest (POI) in response to a UAG stop codon by two commonly used orthogonal archaeal tRNA synthetase and tRNA pairs...
2024: Methods in Molecular Biology
#34
Chloe C Ence, Taher Uddin, Julien Borrel, Payal Mittal, Han Xie, Jochen Zoller, Amit Sharma, Eamon Comer, Stuart L Schreiber, Bruno Melillo, L David Sibley, Arnab K Chatterjee
UNLABELLED: Previous studies have shown that bicyclic azetidines are potent and selective inhibitors of apicomplexan phenylalanine tRNA synthetase (PheRS), leading to parasite growth inhibition in vitro and in vivo , including in models of Toxoplasma infection. Despite these useful properties, additional optimization is required for the development of efficacious treatments of toxoplasmosis from this inhibitor series, in particular to achieve sufficient exposure in the brain. Here, we describe a series of PheRS inhibitors built on a new bicyclic pyrrolidine core scaffold designed to retain the exit-vector geometry of the isomeric bicyclic azetidine core scaffold while offering avenues to sample diverse chemical space...
February 28, 2024: bioRxiv
#35
Aleksandar Radakovic, Anna Lewicka, Marco Todisco, Harry R M Aitken, Zoe Weiss, Shannon Kim, Abdullah Bannan, Joseph A Piccirilli, Jack W Szostak
Coded ribosomal peptide synthesis could not have evolved unless its sequence and amino acid specific aminoacylated tRNA substrates already existed. We therefore wondered whether aminoacylated RNAs might have served some primordial function prior to their role in protein synthesis. Here we show that specific RNA sequences can be nonenzymatically aminoacylated and ligated to produce amino acid-bridged stem-loop RNAs. We used deep sequencing to identify RNAs that undergo highly efficient glycine aminoacylation followed by loop-closing ligation...
March 3, 2024: bioRxiv
#36
Charlotte Roy, Nathalie Allou, Aurore Coulomb, Dominique Grenet, Raphaël Borie, Benjamin Zuber, Abdulmonem Hamid, Matthieu Glorion, Anne-Laure Brun, Elizabeth Longchamps, Alice Hadchouel, Olivier Brugiere
Pulmonary alveolar proteinosis (PAP) results from the accumulation of lipoproteinaceous material in the alveoli and alveolar macrophages, and can be associated with pulmonary fibrosis (PAP-PF), with a need for lung transplantation (LTx). Causes of PAP are autoimmune (90-95%), secondary (5%), or hereditary (<1%). Patients with hereditary PAP are generally not considered for isolated LTx, due to the high probability of recurrence after LTx, and only a challenging scenario with sequential LTx followed by HSCT was reported as successful...
March 8, 2024: American Journal of Transplantation
#37
JOURNAL ARTICLE
Kenichi Matsuda, Toshiyuki Wakimoto
Nitrogen-Nitrogen (N-N) bond-containing functional groups in natural products and synthetic drugs play significant roles in exerting biological activities. The mechanisms of N-N bond formation in natural organic molecules have garnered increasing attention over the decades. Recent advances have illuminated various enzymatic and nonenzymatic strategies, and our understanding of natural N-N bond construction is rapidly expanding. A group of didomain proteins with zinc-binding cupin/methionyl-tRNA synthetase (MetRS)-like domains, also known as hydrazine synthetases, generates amino acid-based hydrazines, which serve as key biosynthetic precursors of diverse N-N bond-containing functionalities such as hydrazone, diazo, triazene, pyrazole, and pyridazinone groups...
March 8, 2024: Chembiochem: a European Journal of Chemical Biology
#38
JOURNAL ARTICLE
Feihu Lu, Kaijiang Xia, Jingtian Su, Jia Yi, Zhiteng Luo, Jun Xu, Qiong Gu, Bingyi Chen, Huihao Zhou
Methionyl-tRNA synthetase (MetRS) catalyzes the attachment of l-methionine (l-Met) to tRNAMet to generate methionyl-tRNAMet , an essential substrate for protein translation within ribosome. Owing to its indispensable biological function and the structural discrepancies with human counterpart, bacterial MetRS is considered an ideal target for developing antibacterials. Herein, chlorhexidine (CHX) was identified as a potent binder of Staphylococcus aureus MetRS (SaMetRS) through an ATP-aided affinity screening...
March 4, 2024: European Journal of Medicinal Chemistry
#39
JOURNAL ARTICLE
Xingli Han, Yamin Gao, Biao Zhou, H M Adnan Hameed, Cuiting Fang, Yanan Ju, Jing He, Xiange Fang, Zhiyong Liu, Wei Yu, Xiaoli Xiong, Nanshan Zhong, Tianyu Zhang
Tuberculosis (TB) is the leading infectious disease caused by Mycobacterium tuberculosis and the second-most contagious killer after COVID-19. The emergence of drug-resistant TB has caused a great need to identify and develop new anti-TB drugs with novel targets. Indole propionic acid (IPA), a structural analog of tryptophan (Trp), is active against M. tuberculosis in vitro and in vivo . It has been verified that IPA exerts its antimicrobial effect by mimicking Trp as an allosteric inhibitor of TrpE, which is the first enzyme in the Trp synthesis pathway of M...
March 8, 2024: ACS Infectious Diseases
#40
JOURNAL ARTICLE
Yuhang Wen, Yadan Luo, Hao Qiu, Baoting Chen, Jingrong Huang, Shuya Lv, Yan Wang, Jiabi Li, Lingling Tao, Bailin Yang, Ke Li, Lvqin He, Manli He, Qian Yang, Zehui Yu, Wudian Xiao, Mingde Zhao, Xiaoxia Zou, Ruilin Lu, Congwei Gu
INTRODUCTION: It is well-known that different populations and animals, even experimental animals with the same rearing conditions, differ in their susceptibility to obesity. The disparity in gut microbiota could potentially account for the variation in susceptibility to obesity. However, the precise impact of gut microbiota on gut metabolites and its subsequent influence on susceptibility to obesity remains uncertain. METHODS: In this study, we established obesity-prone (OP) and obesity-resistant (OR) mouse models by High Fat Diet (HFD)...
2024: Frontiers in Microbiology
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