RNF14-dependent atypical ubiquitylation promotes translation-coupled resolution of RNA-protein crosslinks.

ABSTRACT: Reactive aldehydes are abundant endogenous metabolites that challenge homeostasis by crosslinking cellular macromolecules. Aldehyde-induced DNA damage requires repair to prevent cancer and premature aging, but it is unknown whether cells also possess mechanisms that resolve aldehyde-induced RNA lesions. Here, we establish photoactivatable ribonucleoside-enhanced crosslinking (PAR-CL) as a model system to study RNA crosslinking damage in the absence of confounding DNA damage in human cells. We find that such RNA damage causes translation stress by stalling elongating ribosomes, which leads to collisions with trailing ribosomes and activation of multiple stress response pathways. Moreover, we discovered a translation-coupled quality control mechanism that resolves covalent RNA-protein crossl

SUBMITTER: Zhao S 

PROVIDER: S-EPMC10783637 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature