Response to Shen et al.

Kok, Gautam; Fuchs, Sabine A.

doi:10.1016/j.gim.2021.09.022

Cited by 1 publication

(1 citation statement)

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“…Importantly, these patients still have some intrinsic aminoacylation activity. It is hypothesized that deficiencies in the aaRS enzymes may result in the inability to supply sufficient charged tRNAs to support protein synthesis, especially during periods of increased demand, such as rapid growth and infections ( Kok et al, 2022 ). Knowledge of this disease mechanism led Kok et al to trial a personalized intervention in four patients based on oral supplementation with the cognate amino acid matching the patients’ aaRS deficiency (e.g., the patient with biallelic IARS1 variants received high doses of oral l -isoleucine) ( Kok et al, 2021 ).…”

Section: Human Diseases Associated With Genetic Variants In Aars-enco...mentioning

confidence: 99%

Aminoacyl-tRNA synthetases in human health and disease

Turvey

Horváth²,

Cavalcanti³

2022

Front. Physiol.

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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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Section: Human Diseases Associated With Genetic Variants In Aars-enco...mentioning

confidence: 99%