Aminoacyl-tRNA synthetases in human health and disease

Alexandra K. Turvey; Gabriella A. Horvath; André R. O. Cavalcanti

doi:10.3389/fphys.2022.1029218

journal article Open Access Oct 18, 2022

Aminoacyl-tRNA synthetases in human health and disease

Alexandra K. Turvey Gabriella A. Horvath André R. O. Cavalcanti

Frontiers in Physiology Vol. 13 · Frontiers Media SA

View at Publisher Save 10.3389/fphys.2022.1029218

Abstract

The Aminoacyl-tRNA Synthetases (aaRSs) are an evolutionarily ancient family of enzymes that catalyze the esterification reaction linking a transfer RNA (tRNA) with its cognate amino acid matching the anticodon triplet of the tRNA. Proper functioning of the aaRSs to create aminoacylated (or “charged”) tRNAs is required for efficient and accurate protein synthesis. Beyond their basic canonical function in protein biosynthesis, aaRSs have a surprisingly diverse array of non-canonical functions that are actively being defined. The human genome contains 37 genes that encode unique aaRS proteins. To date, 56 human genetic diseases caused by damaging variants in aaRS genes have been described: 46 are autosomal recessive biallelic disorders and 10 are autosomal dominant monoallelic disorders. Our appreciation of human diseases caused by damaging genetic variants in the aaRSs has been greatly accelerated by the advent of next-generation sequencing, with 89% of these gene discoveries made since 2010. In addition to these genetic disorders of the aaRSs, anti-synthetase syndrome (ASSD) is a rare autoimmune inflammatory myopathy that involves the production of autoantibodies that disrupt aaRS proteins. This review provides an overview of the basic biology of aaRS proteins and describes the rapidly growing list of human diseases known to be caused by genetic variants or autoimmune targeting that affect both the canonical and non-canonical functions of these essential proteins.

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Published: Oct 18, 2022
Vol/Issue: 13
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Authors

André R. O. Cavalcanti

Cite This Article

Alexandra K. Turvey, Gabriella A. Horvath, André R. O. Cavalcanti (2022). Aminoacyl-tRNA synthetases in human health and disease. Frontiers in Physiology, 13. https://doi.org/10.3389/fphys.2022.1029218

Aminoacyl-tRNA synthetases in human health and disease

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