Ageing exacerbates ribosome pausing to disrupt cotranslational proteostasis.

ABSTRACT: Ageing is accompanied by a decline in cellular proteostasis, which underlies many age-related protein misfolding diseases^1,2. Yet, how ageing impairs proteostasis remains unclear. As nascent polypeptides represent a substantial burden on the proteostasis network³, we hypothesized that altered translational efficiency during ageing could help to drive the collapse of proteostasis. Here we show that ageing alters the kinetics of translation elongation in both Caenorhabditis elegans and Saccharomyces cerevisiae. Ribosome pausing was exacerbated at specific positions in aged yeast and worms, including polybasic stretches, leading to increased ribosome collisions known to trigger ribosome-associated quality control (RQC)^4-6. Notably, aged yeast cells exhibited i

SUBMITTER: Stein KC 

PROVIDER: S-EPMC8918044 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature