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)
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)
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)
Review
Clinical Neurology
Denise L. Chan, Joelle Rudinger-Thirion, Magali Frugier, Lisa G. Riley, Gladys Ho, Kavitha Kothur, Shekeeb S. Mohammad
Summary: This article describes a case with milder phenotype caused by QARS1 variants and reviews the association between aminoacyl-tRNA synthetase disorders and epilepsy. Functional testing showed reduced solubility of the QARS1 mutants, but only mild impact on tRNA aminoacylation activity.
BRAIN & DEVELOPMENT
(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)
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
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)
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
Genetics & Heredity
Nina Boegershausen, Hannah E. Krawczyk, Rami A. Jamra, Sheng-Jia Lin, Goekhan Yigit, Irina Huening, Anna M. Polo, Barbara Vona, Kevin Huang, Julia Schmidt, Janine Altmueller, Johannes Luppe, Konrad Platzer, Beate B. Doergeloh, Andreas Busche, Saskia Biskup, Marisa Mendes, Desiree E. C. Smith, Gajja S. Salomons, Arne Zibat, Eva Bueltmann, Peter Nuernberg, Malte Spielmann, Johannes R. Lemke, Yun Li, Martin Zenker, Gaurav K. Varshney, Hauke S. Hillen, Christian P. Kratz, Bernd Wollnik
Summary: Aminoacylation of tRNA is a crucial step in protein biosynthesis and is associated with various genetic disorders. This study reports five individuals with biallelic missense variants in WARS1 or SARS1, who exhibited similar phenotypes including microcephaly, developmental delay, intellectual disability, and brain anomalies. The identified variants were found to negatively affect protein function, providing functional insights into the pathogenesis of WARS1-related syndrome and expanding the disease spectrum of ARS-related developmental disorders with or without microcephaly.
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
Immunology
Yoshinao Muro, Yasuhiko Yamano, Ken Yoshida, Yohsuke Oto, Kimiko Nakajima, Teruyuki Mitsuma, Shiori Kikuchi, Akihiro Matsumae, Mariko Ogawa-Momohara, Takuya Takeichi, Yasuhiro Kondoh, Masao Katayama, Yasuyuki Todoroki, Yoshiya Tanaka, Minoru Satoh, Masashi Akiyama
Summary: This study aimed to establish an ELISA method for detecting anti-OJ antibodies using KARS and IARS recombinant proteins. The results showed that the ELISA method had high sensitivity and specificity, with a high agreement with immunoprecipitation results.
JOURNAL OF AUTOIMMUNITY
(2021)
Article
Medicine, General & Internal
Kyungjong Lee, Mijung Oh, Kyo-Sun Lee, Yoon Jin Cha, Yoon Soo Chang
Summary: The combination of MARS staining with conventional cytology showed increased diagnostic accuracy for diagnosing lung nodules suspected of lung cancer on chest-computed tomography scans.
Review
Biochemistry & Molecular Biology
Jyoti Chhibber-Goel, Manickam Yogavel, Amit Sharma
Summary: Malaria, caused by parasitic protists, affects over 3 billion people globally with drug resistance posing a major threat to treatment. Targeting aminoacyl-tRNA synthetases (aaRSs) as antimalarial drug targets shows promising potential in killing malaria parasites selectively. This approach highlights the need for new alternatives in malaria treatment to combat drug resistance.
Editorial Material
Clinical Neurology
Maryam Oskoui, Hernan Gonorazky, Hugh J. McMillan, James J. Dowling, Reshma Amin, Cynthia Gagnon, Kathryn Selby
CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES
(2022)
Article
Clinical Neurology
Kristina M. Joyal, Jessica MacGregor, Lamia M. Hayawi, Richard J. Webster, Hugh J. McMillan
Summary: This study reviewed the volume and referral sources of nerve conduction studies (NCS) and electromyography (EMG) at a pediatric tertiary care hospital from 2014 to 2019. The findings indicate that NCS/EMG remains a valuable diagnostic tool, especially for acquired neuromuscular conditions, and can be well tolerated in children of all ages without the need for sedation.
CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES
(2022)
Letter
Clinical Neurology
Kristin D. Kernohan, Hugh J. McMillan, Ed Yeh, Melanie Lacaria, Michael Kowalski, Craig Campbell, James J. Dowling, Hernan Gonorazky, Janet Marcadier, Mark A. Tarnopolsky, Jiri Vajsar, Alex Mackenzie, Pranesh Chakraborty
CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES
(2022)
Article
Biotechnology & Applied Microbiology
Hugh J. McMillan, Crystal M. Proud, Michelle A. Farrar, Ian E. Alexander, Francesco Muntoni, Laurent Servais
Summary: Gene therapy for spinal muscular atrophy (SMA) is a significant advancement in the treatment of neurologic diseases. Onasemnogene abeparvovec, a one-time gene replacement therapy, has shown improved survival and motor milestones for SMA patients. However, gene therapy is still in its early stages and faces challenges in transgene delivery.
EXPERT OPINION ON BIOLOGICAL THERAPY
(2022)
Article
Cardiac & Cardiovascular Systems
William J. Groh, Deepak Bhakta, Gordon F. Tomaselli, Ryan G. Aleong, Ricardo Alkmim Teixeira, Anthony Amato, Samuel J. Asirvatham, Yong-Mei Cha, Domenico Corrado, Denis Duboc, Zachary D. Goldberger, Minoru Horie, Joseph E. Hornyak, John Lynn Jefferies, Stefan Kaab, Jonathan M. Kalman, Naomi J. Kertesz, Neal K. Lakdawala, Pier D. Lambiase, Steven A. Lubitz, Hugh J. McMillan, Elizabeth M. McNally, Margherita Milone, Narayanan Namboodiri, Saman Nazarian, Kristen K. Patton, Vincenzo Russo, Frederic Sacher, Pasquale Santangeli, Win-Kuang Shen, Dario C. Sobral Filho, Bruce S. Stambler, Claudia Stollberger, Karim Wahbi, Xander H. T. Wehrens, Menachem Mendel Weiner, Matthew T. Wheeler, Katja Zeppenfeld
Summary: This document provides guidance for healthcare professionals in caring for patients with arrhythmic complications of neuromuscular disorders. It presents an overview of arrhythmias in different neuromuscular disorders and emphasizes the importance of managing arrhythmic cardiac manifestations.
Article
Medicine, General & Internal
Michela Guglieri, Kate Bushby, Michael P. McDermott, Kimberly A. Hart, Rabi Tawil, William B. Martens, Barbara E. Herr, Elaine McColl, Chris Speed, Jennifer Wilkinson, Janbernd Kirschner, Wendy M. King, Michelle Eagle, Mary W. Brown, Tracey Willis, Robert C. Griggs
Summary: A double-blind, parallel-group randomized clinical trial was conducted to compare the efficacy and adverse effects of different corticosteroid regimens in boys with Duchenne muscular dystrophy. The study found that daily prednisone and daily deflazacort were more effective than intermittent prednisone for improving motor function, pulmonary function, and satisfaction with treatment over a 3-year period. There was no significant difference between the two daily corticosteroid regimens.
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
(2022)
Correction
Genetics & Heredity
Lijia Huang, Jodi Warman-Chardon, Melissa T. Carter, Kathie L. Friend, Tracy E. Dudding, Jeremy Schwartzentruber, Ruobing Zou, Peter W. Schofield, Stuart Douglas, Dennis E. Bulman, Kym M. Boycott
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Multidisciplinary Sciences
Jenny Setchell, Donya Mosleh, Laura McAdam, Patricia Thille, Thomas Abrams, Hugh J. McMillan, Bhavnita Mistry, Barbara E. Gibson
Summary: This paper evaluates a study that aimed to enhance clinical care for patients with muscular dystrophy and their families through regular dialogues with clinicians. The study found that the intervention led to changes in the clinical teams' thinking and practices regarding the emotional, social, and experiential aspects of living with the disease. However, there were differences between clinicians and clinics in the extent of these changes.
Article
Respiratory System
Sherri L. Katz, Jean K. Mah, Hugh J. McMillan, Craig Campbell, Vid Bijelic, Nick Barrowman, Franco Momoli, Henrietta Blinder, Shawn D. Aaron, Laura C. McAdam, The Thanh Diem Nguyen, Mark Tarnopolsky, David F. Wensley, David Zielinski, Louise Rose, Nicole Sheers, David J. Berlowitz, Lisa Wolfe, Doug McKim
Summary: This randomized controlled trial aimed to determine whether twice-daily lung volume recruitment (LVR) therapy attenuates the decline in forced vital capacity (FVC) at 2 years in boys with Duchenne muscular dystrophy (DMD). The results showed that there was no difference in decline in FVC with the use of twice-daily LVR for boys with relatively normal lung function.
Article
Biochemistry & Molecular Biology
Kevin A. Strauss, Michelle A. Farrar, Francesco Muntoni, Kayoko Saito, Jerry R. Mendell, Laurent Servais, Hugh J. McMillan, Richard S. Finkel, Kathryn J. Swoboda, Jennifer M. Kwon, Craig M. Zaidman, Claudia A. Chiriboga, Susan T. Iannaccone, Jena M. Krueger, Julie A. Parsons, Perry B. Shieh, Sarah Kavanagh, Melissa Wigderson, Sitra Tauscher-Wisniewski, Bryan E. McGill, Thomas A. Macek
Summary: Onasemnogene abeparvovec was effective and well tolerated for presymptomatic infants at risk of SMA type 2, underscoring the urgency of early identification and intervention.
Article
Biochemistry & Molecular Biology
Kevin A. Strauss, Michelle A. Farrar, Francesco Muntoni, Kayoko Saito, Jerry R. Mendell, Laurent Servais, Hugh J. McMillan, Richard S. Finkel, Kathryn J. Swoboda, Jennifer M. Kwon, Craig M. Zaidman, Claudia A. Chiriboga, Susan T. Iannaccone, Jena M. Krueger, Julie A. Parsons, Perry B. Shieh, Sarah Kavanagh, Sitra Tauscher-Wisniewski, Bryan E. McGill, Thomas A. Macek
Summary: SPR1NT (NCT03505099) is a Phase III study investigating the efficacy and safety of onasemnogene abeparvovec in presymptomatic children with biallelic SMN1 mutations. The results showed that all 14 infants enrolled in the study were able to sit independently for at least 30 seconds within 18 months and none required permanent ventilation. The treatment was well tolerated and effective for children expected to develop SMA type 1.
Article
Cardiac & Cardiovascular Systems
Di Yu, Nuanyi Liang, Julia Zebarth, Qing Shen, Miracle Ozzoude, Maged Goubran, Jennifer S. Rabin, Joel Ramirez, Christopher J. M. Scott, Fuqiang Gao, Robert Bartha, Sean Symons, Seyyed Mohammad Hassan Haddad, Courtney Berezuk, Brian Tan, Donna Kwan, Robert A. Hegele, Allison A. Dilliott, Nuwan D. Nanayakkara, Malcolm A. Binns, Derek Beaton, Stephen R. Arnott, Jane M. Lawrence-Dewar, Ayman Hassan, Dar Dowlatshahi, Jennifer Mandzia, Demetrios Sahlas, Leanne Casaubon, Gustavo Saposnik, Yurika Otoki, Krista L. Lanctot, Mario Masellis, Sandra E. Black, Richard H. Swartz, Ameer Y. Taha, Walter Swardfager
Summary: A study found that cerebral small vessel disease is associated with the ratio of certain fatty acid metabolites, and this association has not been examined in stroke patients before. The study analyzed clinical and imaging data of stroke patients and found that the ratio of these fatty acid metabolites is related to small vessel stroke, white matter hyperintensities, and temporal lobe atrophy.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Meeting Abstract
Endocrinology & Metabolism
Stefan Jackowski, Utkarsh Dang, Jinhui Ma, Maya Scharke, Victor Konji, Jacob Jaremko, Khaldoun Koujok, Mary-Ann Matzinger, Nazih Shenouda, Scott Walker, Colleen Hartigan, Lynn MacLeay, Nasrin Khan, Elizabeth Sykes, Hugh McMillan, Kerry Siminoski, Pradeep Bista, Maria Mancini, Joanne Donovan, Leanne Ward
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)
Meeting Abstract
Endocrinology & Metabolism
Stefan Jackowski, Utkarsh Dang, Maya Scharke, Victor Konji, Jacob Jaremko, Khaldoun Koujok, Mary-Ann Matzinger, Nazih Shenouda, Nasrin Khan, Lynn MacLeay, Elizabeth Sykes, Hugh McMillan, Kerry Siminoski, Paula Clemens, Michela Guglieri, Jean Mah, Eric Hoffman, Leanne Ward
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Irit Hochberg, Leigh A. M. Demain, Julie Richer, Kyle Thompson, Waheeda Pagarkar, Agusti Rodriguez-Palmero Seuma, Edgard Verdura, Aurora Pujol, Albert Amberger, Andrea J. Deutschmann, Sandra Demetz, James O'Sullivan, Meredith Gillespie, Inna A. Belyantseva, Hugh J. McMillan, Melanie Barzik, Jill E. Urquhart, Alessandro Rea, Glenda M. Beaman, Simon G. Williams, Sanjeev S. Bhaskar, Isabella R. Lawrence, Emma M. Jenkinson, Jessica L. Zambonin, Zeev Blumenfeld, Sergey Yalonetsky, Stephanie Oerum, Walter Rossmanith, Wyatt W. Yue, Johannes Zschocke, Kevin J. Munro, Brendan J. Battersby, Thomas B. Friedman, Robert W. Taylor, Raymond T. O'Keefe, William G. Newman
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)