Ribosome profiling reveals a functional role for autophagy in mRNA 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 autophagy influences the protein synthesis landscape in mammalian cells remains unclear. Here, we utilize ribosome profiling to delineate the effects of genetic ablation of the autophagy regulator, ATG12, on 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 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 that autophagy impacts protein translation and shapes the protein landscape.
Goldsmith et al. employ ribosome profiling to dissect how deletion of the essential autophagy component Atg12 impacts mRNA translation. They detect changes in the translation of mRNAs involved in DNA repair, centrosome clustering and cell cycle control and specifically focus on how loss of autophagy causes reduced production of BRCA2 and increased DNA damage.