Evidence for a dominant-negative mechanism in HARS1-mediated peripheral neuropathy

FEBS J. 2021 Jan;288(1):91-94. doi: 10.1111/febs.15538. Epub 2020 Sep 17.

Abstract

The pathogenic mechanism of neuropathy-associated aminoacyl-tRNA synthetase (ARS) gene variants is poorly defined. Mullen et al. generate new models of pathogenic, dominant HARS1 mutations and show that they increase eIF2α phosphorylation and decrease protein translation in neurons. These results are consistent with a dominant-negative mechanism of ARS-mediated peripheral neuropathy. Comment on: https://doi.org/10.1111/febs.15449.

Keywords: HARS1; aminoacyl-tRNA synthetase; dominant-negative; peripheral neuropathy; protein translation.

Publication types

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

MeSH terms

  • Animals
  • Histidine-tRNA Ligase*
  • Mutation
  • Neuronal Outgrowth
  • Peripheral Nervous System Diseases* / genetics
  • Protein Biosynthesis
  • Zebrafish

Substances

  • Histidine-tRNA Ligase