Unresolved stalled ribosome complexes restrict cell-cycle progression after genotoxic stress.

ABSTRACT: During the translation surveillance mechanism known as ribosome-associated quality control, the ASC-1 complex (ASCC) disassembles ribosomes stalled on the mRNA. Here, we show that there are two distinct classes of stalled ribosome. Ribosomes stalled by translation elongation inhibitors or methylated mRNA are short lived in human cells because they are split by the ASCC. In contrast, although ultraviolet light and 4-nitroquinoline 1-oxide induce ribosome stalling by damaging mRNA, and the ASCC is recruited to these stalled ribosomes, we found that they are refractory to the ASCC. Consequently, unresolved UV- and 4NQO-stalled ribosomes persist in human cells. We show that ribosome stalling activates cell-cycle arrest, partly through ZAK-p38^MAPK signaling, and that this cell-cycle

SUBMITTER: Stoneley M 

PROVIDER: S-EPMC9098122 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature