Specific branches of the proteostasis network regulate the toxicity associated with mistranslation.

ABSTRACT: All cellular functions rely on accurate protein biosynthesis. Yet, many variants of transfer RNA (tRNA) genes that induce amino acid misincorporation are found in human genomes. Mistranslation induces pleiotropic effects on proteostasis, ranging from protein misfolding to impaired protein biosynthesis and degradation. We employ Saccharomyces cerevisiae (budding yeast), a genetically and biochemically tractable model that facilitates quantitative analysis of how specific proteostasis pathways interact with mistranslating tRNAs. We tested two mistranslating tRNASer variants, one inducing proline to serine (P > S), the other arginine to serine (R > S) misincorporation. We found that P > S misincorporation impairs cellular fitness and sensitizes cells to protein misfolding to a greater extent

SUBMITTER: McDonald DW 

PROVIDER: S-EPMC12082455 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature