Human aminoacyl-tRNA synthetases in diseases of the nervous system

RNA Biol. 2018;15(4-5):623-634. doi: 10.1080/15476286.2017.1330245. Epub 2017 Jun 30.


Aminoacyl-tRNA synthetases (AaRSs) are ubiquitously expressed enzymes that ensure accurate translation of the genetic information into functional proteins. These enzymes also execute a variety of non-canonical functions that are significant for regulation of diverse cellular processes and that reside outside the realm of protein synthesis. Associations between faults in AaRS-mediated processes and human diseases have been long recognized. Most recent research findings strongly argue that 10 cytosolic and 14 mitochondrial AaRSs are implicated in some form of pathology of the human nervous system. The advent of modern whole-exome sequencing makes it all but certain that similar associations between the remaining 15 ARS genes and neurologic illnesses will be defined in future. It is not surprising that an intense scientific debate about the role of translational machinery, in general, and AaRSs, in particular, in the development and maintenance of the healthy human neural cell types and the brain is sparked. Herein, we summarize the current knowledge about causative links between mutations in human AaRSs and diseases of the nervous system and briefly discuss future directions.

Keywords: Aminoacyl-tRNA synthetase; encephalopathy; mutation; neurodegenerative disease; neuropathy; ponto-cerebellar hypoplasia; tRNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Amino Acyl-tRNA Synthetases / genetics*
  • Amino Acyl-tRNA Synthetases / metabolism
  • Brain Diseases / enzymology
  • Brain Diseases / genetics*
  • Brain Diseases / pathology
  • Cerebellar Diseases / enzymology
  • Cerebellar Diseases / genetics*
  • Cerebellar Diseases / pathology
  • Cranial Nerve Diseases / enzymology
  • Cranial Nerve Diseases / genetics*
  • Cranial Nerve Diseases / pathology
  • Cytosol / metabolism
  • Gene Expression
  • Humans
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Mutation*
  • Nervous System / enzymology
  • Nervous System / pathology
  • RNA, Transfer / genetics*
  • RNA, Transfer / metabolism


  • Mitochondrial Proteins
  • RNA, Transfer
  • Amino Acyl-tRNA Synthetases

Supplementary concepts

  • Pontocerebellar Hypoplasia