Genetic Interaction of tRNA-Dependent Mistranslation with Fused in Sarcoma Protein Aggregates.

ABSTRACT: High-fidelity protein synthesis requires properly aminoacylated transfer RNAs (tRNAs), yet diverse cell types, from bacteria to humans, show a surprising ability to tolerate errors in translation resulting from mutations in tRNAs, aminoacyl-tRNA synthetases, and other components of protein synthesis. Recently, we characterized a tRNA^Ser_AGA G35A mutant (tRNA^Ser_AAA) that occurs in 2% of the human population. The mutant tRNA decodes phenylalanine codons with serine, inhibits protein synthesis, and is defective in protein and aggregate degradation. Here, we used cell culture models to test our hypothesis that tRNA-dependent mistranslation will exacerbate toxicity caused by amyotrophic lateral sclerosis (ALS)-associated protein aggregation. Relative t

SUBMITTER: Lant JT 

PROVIDER: S-EPMC9956149 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature