Ribosome profiling reveals a functional role for autophagy in protein translational control

Autophagy promotes protein degradation, and therefore has been proposed to
maintain amino acid pools to sustain protein synthesis during metabolic
stress. To date, how the autophagy pathway influences the protein
translational landscape in mammalian cells remains unclear. Here, we
utilize ribosome profiling to delineate the effects of genetic ablation of
the autophagy regulator, ATG12, on protein translational control. In
mammalian cells, genetic loss of autophagy does not impact global rates of
cap dependent translation, even under starvation conditions. Instead,
autophagy supports the translation of a subset of mRNAs with complex 5’UTR
structures, enriched for cell cycle control and DNA damage repair. In
particular, we demonstrate that autophagy enables the translation of the
DNA damage repair protein BRCA2, which is functionally required to
attenuate DNA damage and promote cell survival in response to PARP
inhibition.  Overall, our findings illuminate a new role for
autophagy directing the protein translational landscape.