Article
Biochemistry & Molecular Biology
Jessica M. Warren, Amanda K. Broz, Ana Martinez-Hottovy, Christian Elowsky, Alan C. Christensen, Daniel B. Sloan
Summary: The number of tRNAs encoded in plant mitochondrial genomes varies considerably. The loss of bacterial-like mitochondrial tRNA genes necessitates the import of nuclear-encoded counterparts with little sequence similarity. The evolution of aaRS subcellular localization in Sileneae reveals differing constraints on tRNA/aaRS interactions and alternative coevolutionary paths for maintaining organellar translation in plant cells.
MOLECULAR BIOLOGY AND EVOLUTION
(2023)
Letter
Immunology
Yoshinao Muro, Yuta Yamashita, Haruka Koizumi, Mariko Ogawa-Momohara, Takuya Takeichi, Teruyuki Mitsuma, Masashi Akiyama
Summary: Anti-aminoacyl-tRNA synthetase (anti-ARS) antibodies are helpful in identifying inflammatory myopathy patients. In a study with Japanese patients, autoantibodies against CysARS and ValARS were found in the serum of two dermatomyositis patients. One patient showed features of anti-synthetase syndrome, while the other did not. Further research is needed to explore the clinical differences among different anti-ARS antibodies.
AUTOIMMUNITY REVIEWS
(2022)
Article
Oncology
Krishnendu Khan, Valentin Gogonea, Paul L. Fox
Summary: Aminoacyl-tRNA synthetases (AARS) are important enzymes in mammalian cells that play a key role in protein translation. Recent studies have found that they exist in the cytoplasmic multi-tRNA synthetase complex (MSC) and have non-canonical functions in addition to their role in protein translation. These findings have the potential to be new therapeutic targets for cancer and other diseases.
TRANSLATIONAL ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Chen Yuan, Zihan Li, Xinyu Luo, Pingping Huang, Lijie Guo, Meiling Lu, Jie Xia, Yibei Xiao, Xiao-Long Zhou, Meirong Chen
Summary: tRNA aminoacylation is a highly regulated process that determines translation fidelity. Previous studies have shown the propensity of eukaryotic AlaRS to mischarge tRNACys and tRNAThr with alanine. This study demonstrates that mouse ProXp-ala can efficiently correct mischarged Ala-tRNAThr, providing insights into the translation quality control mechanism in higher eukaryotic organisms.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
Siqi Wu, Li Zheng, Zhoufei Hei, Jing-Bo Zhou, Guang Li, Peifeng Li, Jiayuan Wang, Hamid Ali, Xiao-Long Zhou, Jing Wang, Pengfei Fang
Summary: The structures of human Lysyl-tRNA synthetases (LysRSs) are more dynamic than those from single-celled organisms. Without the presence of MSC scaffold proteins, human LysRS can exist independently from the multi-tRNA synthetase complex (MSC). The interaction with the scaffold protein AIMP2 stabilizes the closed conformation of LysRS and protects its essential aminoacylation activity under stressed conditions. Deleting AIMP2 from human cells leads to slow cell growth in nutrient deficient mediums. These results suggest that the evolutionary emergence of the MSC in metazoan might be to protect the aminoacyl-tRNA synthetase components from being modified or recruited for use in other cellular pathways.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Review
Genetics & Heredity
Tamara L. Hendrickson, Whitney N. Wood, Udumbara M. Rathnayake
Summary: The selection of the twenty amino acids in the standard genetic code and the fixation of aminoacyl-tRNA synthetases (aaRSs) before LUCA were influenced by the chemical reactivity of amino acid side chains. Some amino acid properties delayed or prohibited the emergence of corresponding aaRSs, playing critical roles in defining the amino acids in the genetic code.
Article
Biochemistry & Molecular Biology
Chong Dai, Adriana Reyes-Ordonez, Jae-Sung You, Jie Chen
Summary: Aminoacyl-tRNA synthetases play essential roles in protein synthesis, with some also exhibiting non-translational functions. Threonyl-tRNA synthetase (ThrRS) has been found to negatively regulate myoblast differentiation through a non-catalytic mechanism involving new domains UNE-T and TGS. ThrRS interacts with Axin1, inhibiting JNK signaling and affecting skeletal myogenesis through the MEKK4-MKK4-JNK pathway.
Article
Multidisciplinary Sciences
Krishnendu Khan, Briana Long, Valentin Gogonea, Gauravi M. Deshpande, Kommireddy Vasu, Paul L. Fox
Summary: Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes in the translation process that ligate amino acids to their corresponding transfer RNAs (tRNAs). In mammalian cells, these enzymes, along with AIMPs proteins, form a large multi-tRNA synthetase complex (MSC), whose assembly mechanism and function are still unclear. This study reveals the importance of cotranslational interactions, particularly involving AIMPs proteins, in the assembly process of the MSC. Interestingly, these cotranslational interactions sometimes involve more than two proteins, suggesting a diverse pathway for the ordered assembly of small subcomplexes into larger complexes.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Immunology
Angeles S. Galindo-Feria, Antonella Notarnicola, Ingrid E. Lundberg, Begum Horuluoglu
Summary: Anti-synthetase syndrome is an autoimmune disease characterized by the presence of autoantibodies targeting aminoacyl t-RNA synthetases along with various clinical features. This review summarizes the functions of aaRSs, their autoantigenic properties, and their association with ASSD.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Mohamed M. Aboelnga, James W. Gauld
Summary: This study aims to evaluate the binding proficiency of potential inhibitors against threonyl-tRNA synthetases. Through quantum chemical study, binding energy value comparison, and molecular docking, several potent ligands have been suggested, which could be valuable in developing competitive inhibitors against bacterial ThrRS.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Review
Biochemistry & Molecular Biology
Swadha Gupta, Jaykumar Jani, Jigneshkumar Vijayasurya, Jigneshkumar Mochi, Saba Tabasum, Akash Sabarwal, Anju Pappachan
Summary: Aminoacyl-tRNA synthetases (AaRSs) play essential roles in translating genetic information and have diverse functions in cellular activities such as transcription, apoptosis, angiogenesis, inflammation, and cancer. Their multifunctionality suggests their potential as therapeutic targets.
Article
Biochemistry & Molecular Biology
Nien-Ching Han, Arundhati Kavoor, Michael Ibba
Summary: Editing mechanisms are crucial for correct amino acid incorporation during protein synthesis. Editing-deficient aaRSs have been found in host-dependent organisms. In this study, a previously unknown hyperaccurate mutation, L287F, was identified in the amino acid activation site of MmPheRS. It was also discovered that m-Tyr, a toxic oxidation byproduct of Phe, is poorly discriminated by MmPheRS activation and is not subjected to editing. Furthermore, expressing MmPheRS and the hyperaccurate variants makes E. coli susceptible to m-Tyr stress.
Article
Biochemistry & Molecular Biology
Jose R. Jaramillo Ponce, Anne Theobald-Dietrich, Philippe Benas, Caroline Paulus, Claude Sauter, Magali Frugier
Summary: tRip is a specific tRNA import protein for Plasmodium. It can associate with three aminoacyl-tRNA synthetases (aaRS) and form multi-aaRS complexes (MSC) in the parasite. The crystal structure of the N-terminal GST-like domain of one of the aaRS was solved, allowing further investigation of the solution architecture of the complexes. The biological impact of these structural arrangements is discussed.
Article
Genetics & Heredity
Andrea Accogli, Sheng-Jia Lin, Mariasavina Severino, Sung-Hoon Kim, Kevin Huang, Clarissa Rocca, Megan Landsverk, Maha S. Zaki, Almundher Al-Maawali, Varunvenkat M. Srinivasan, Khalid Al-Thihli, G. Bradly Schaefer, Monica Davis, Davide Tonduti, Chiara Doneda, Lara M. Marten, Chris Muehlhausen, Maria Gomez, Eleonora Lamantea, Rafael Mena, Mathilde Nizon, Vincent Procaccio, Amber Begtrup, Aida Telegra, Hong Cui, Heidi L. Schulz, Julia Mohr, Saskia Biskup, Mariana Amina Loos, Hilda Veronica Araoz, Vincenzo Salpietro, Laura Davis Keppen, Manali Chitre, Cassidy Petree, Lucy Raymond, Julie Vogt, Lindsey B. Sawyer, Alice A. Basinger, Signe Vandal Pedersen, Toni S. Pearson, Dorothy K. Grange, Lokesh Lingappa, Paige Mcdunnah, Rita Horvath, Benjamin Cogne, Bertrand Isidor, Andreas Hahn, Karen W. Gripp, Seyed Mehdi Jafarnejad, Elsebet Stergaard, Carlos E. Prada, Daniele Ghezzi, Vykuntaraju K. Gowda, Robert W. Taylor, Nahum Sonenberg, Henry Houlden, Marie Sissler, Gaurav K. Varshney, Reza Maroofian
Summary: This study reports 18 new individuals with biallelic TARS2 variants, who exhibit developmental delay/intellectual disability, regression, cerebellar and cerebral atrophy, basal ganglia signal alterations, hypotonia, cerebellar signs, and increased blood lactate.
GENETICS IN MEDICINE
(2023)
Article
Neurosciences
Ling-yue Kong, Yi-ze Wu, Run-qi Cheng, Pei-han Wang, Bi-wen Peng
Summary: Mitochondria play a vital role in cellular energy production and contain mitochondrial DNA (mt DNA) responsible for synthesizing respiratory chain components. Dysfunctions in mt DNA translation have been linked to various syndromes, but their precise mechanisms and implications remain to be determined. Mitochondrial tRNAs (mt tRNAs) encoded by mt DNA are known to contribute to mitochondrial dysfunction and are associated with a wide range of pathologies, including epilepsy. This review focuses on the function of mt tRNA and the role of mitochondrial aminoacyl-tRNA synthetase (mt aaRS) in summarizing common mt aaRS mutant genes causing epilepsy and the specific symptoms associated with these diseases.
MOLECULAR NEUROBIOLOGY
(2023)