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Evidence for a dominant‐negative mechanism in HARS1 ‐mediated peripheral neuropathy
Author(s) -
MeyerSchuman Rebecca,
Antonellis Anthony
Publication year - 2021
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.15538
Subject(s) - mechanism (biology) , peripheral neuropathy , translation (biology) , phosphorylation , peripheral , gene , eukaryotic translation , genetics , biology , neuroscience , medicine , messenger rna , endocrinology , philosophy , epistemology , diabetes mellitus
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.