Inhibition of the nucleolar RNA exosome facilitates adaptation to starvation

Abstract

In response to nutrient scarcity, cells must reallocate their limited energy for cellular maintenance at the expense of certain processes. How such a tradeoff is achieved remains largely unknown. RNA surveillance is crucial for the integrity of the transcriptome, whose defects are associated with several human diseases. Unexpectedly, we discover that the nucleolar RNA exosome, a key RNA surveillance machine, is inhibited by starvation. This is not merely the cessation of a temporarily non-essential process, but rather a key signal to allocate energy. By rewiring one-carbon metabolism, the inhibition of RNA exosome reduces translation, the most energy-consuming process. Energy is then conserved for fat synthesis to enhance cellular maintenance and starvation survival. Notably, while benefiting starvation fitness, RNA exosome inhibition impairs the life span of well-fed animals, indicating a tradeoff between short-term and long-term fitness. Our findings suggest that the nucleolar RNA surveillance can be temporarily sacrificed to facilitate starvation adaptation.