Comprehensive assessment of recessive, pathogenic <i>AARS1</i> alleles in a humanized yeast model reveals loss-of-function and dominant-negative effects.

ABSTRACT: Alanyl-tRNA synthetase 1 (AARS1) encodes the enzyme that ligates tRNA molecules to alanine in the cytoplasm, which is required for protein translation. Variants in AARS1 have been implicated in early-onset, multi-system recessive phenotypes and in later-onset dominant peripheral neuropathy; to date, no single variant has been associated with both dominant and recessive diseases raising questions about shared mechanisms between the two inheritance patterns. AARS1 variants associated with recessive disease are predicted to result in null or hypomorphic alleles and this has been demonstrated, in part, via yeast complementation assays. However, pathogenic alleles have not been assessed in a side-by-side manner to carefully scrutinize the strengths and limitations of this m

SUBMITTER: Kuo ME 

PROVIDER: S-EPMC11230197 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature