mTOR-NAA10-C7orf50 axis senses nutritional status to coordinate ribosome biogenesis and autophagy

Cellular metabolism is precisely regulated in response to nutrient availability. As an extremely energy-consuming anabolic process, ribosome biogenesis should be tightly controlled in response to nutrient supply. However, how the nucleolus responds to different nutrient statuses remains poorly understood. Here, we show that C7orf50 is a nucleolus-localized protein and functions as a coordinator between ribosome biogenesis and Autophagy, acting as what we term a "nutrient-responding nucleolar factor." C7orf50 undergoes reversible nucleolus-nucleoplasm translocation in response to nutrient deprivation and supply, with its nucleolus and nucleoplasm location dictating ribosome biogenesis and autophagic augmentation, respectively. The location-dependent function of C7orf50 is determined by acetylation at the lysine-71/lysine-72/lysine-76 residues by N-alpha-acetyltransferase 10, a substrate of mammalian target of rapamycin and a nutritional status-responsive acetyltransferase. In vivo and in vitro assays show that C7orf50 acts as an oncoprotein that promotes tumor growth. Our findings reveal a nucleolus-localized coordinating mechanism for the regulation of anabolism and catabolism transition by nutrient status.