Aminoacyl-tRNA synthetases (aaRSs) catalyze the reaction of amino acids to their cognate transfer RNAs (tRNAs) in protein synthesis. However, these proteins in eukaryotes are an essential part of the translation apparatus and have new roles associated with their nuclear and secreted extracellular forms. Although these novel functions were thought to be 'moonlighting activities', many are critical in physiological and pathological events. Throughout evolution, aaRSs have appended new domains or motifs with no apparent connection to their aminoacylation reactions. The new domains play important roles, at least in part, in angiogenesis, immune response, inflammation, apoptosis and neural development and others.
Firstly, aaRSs have been largely implied in many neuropathies. Some aaRS genes are strongly linked to Charcot-Marie-Tooth (CMT), one of the most common inherited neuromuscular disorders. Nonetheless, the roles of aaRSs in the pathogenesis of CMT remain unclear, and no effective therapies have thus far been developed. In addition, variants of cars genes are also associated with central nervous system disorders, including leukoencephalopathy, early-onset encephalopathy, fatal neurodegenerative syndrome and abnormality in sensory nerve. However, the pathogenesis of these disorders is yet to be studied.
Secondly, aaRSs have been characterized as cellular sensors or immunoregulators in viral infections. Given a close link between aaRSs and viruses, we speculate that aaRSs may play certain noncanonical roles upon viral infections, thus offering treatment discovery and development in human viral infections.
Lastly, the expression and modification of aaRSs have already been characterized in multiple types of cancers. Increasing evidence has linked aaRSs with cancers through their enzymatic roles in protein synthesis and noncanonical functions. However, the biological functions of aaRSs in the initiation and development of many human cancers, especially haematological malignancies, are still missing. Nor is clear about the correlation of human aaRSs with tumour suppressors or oncogenes.
Considering these potential noncanonical roles of aaRSs, this research topic will focus on aaRSs and their interaction partners, including, but not limited to, neuropathies, viral infections and cancers, with an emphasis on their noncanonical roles beyond tRNA aminoacylation. We invite reviews, research articles, and short communications on topics related to these noncanonical functions.
Aminoacyl-tRNA synthetases (aaRSs) catalyze the reaction of amino acids to their cognate transfer RNAs (tRNAs) in protein synthesis. However, these proteins in eukaryotes are an essential part of the translation apparatus and have new roles associated with their nuclear and secreted extracellular forms. Although these novel functions were thought to be 'moonlighting activities', many are critical in physiological and pathological events. Throughout evolution, aaRSs have appended new domains or motifs with no apparent connection to their aminoacylation reactions. The new domains play important roles, at least in part, in angiogenesis, immune response, inflammation, apoptosis and neural development and others.
Firstly, aaRSs have been largely implied in many neuropathies. Some aaRS genes are strongly linked to Charcot-Marie-Tooth (CMT), one of the most common inherited neuromuscular disorders. Nonetheless, the roles of aaRSs in the pathogenesis of CMT remain unclear, and no effective therapies have thus far been developed. In addition, variants of cars genes are also associated with central nervous system disorders, including leukoencephalopathy, early-onset encephalopathy, fatal neurodegenerative syndrome and abnormality in sensory nerve. However, the pathogenesis of these disorders is yet to be studied.
Secondly, aaRSs have been characterized as cellular sensors or immunoregulators in viral infections. Given a close link between aaRSs and viruses, we speculate that aaRSs may play certain noncanonical roles upon viral infections, thus offering treatment discovery and development in human viral infections.
Lastly, the expression and modification of aaRSs have already been characterized in multiple types of cancers. Increasing evidence has linked aaRSs with cancers through their enzymatic roles in protein synthesis and noncanonical functions. However, the biological functions of aaRSs in the initiation and development of many human cancers, especially haematological malignancies, are still missing. Nor is clear about the correlation of human aaRSs with tumour suppressors or oncogenes.
Considering these potential noncanonical roles of aaRSs, this research topic will focus on aaRSs and their interaction partners, including, but not limited to, neuropathies, viral infections and cancers, with an emphasis on their noncanonical roles beyond tRNA aminoacylation. We invite reviews, research articles, and short communications on topics related to these noncanonical functions.
