TORC1 Activates Dormant Ribosomes

When nutrients are limited, cells keep a pool of dormant ribosomes which get activated, when nutrients become available again. The lab of Michael Hall now found that in yeast the protein Stm1 controls the formation of dormant ribosomes. When nutrients become availalbe again TORC1 phosporylates Stm1 which leads to its inhibition and the activation of the dormant ribosomes. They could show that the mammalian ortholog of Stm1 called SERBP1 also regulates the formation of dormant ribosomes. Their findings were published in the article " TORC1 phosphorylates and inhibits the ribosome preservation factor Stm1 to activate dormant ribosomes " in the EMBO Journal.

Synposis
Preservation of a pool of dormant ribosomes under nutrient-limited conditions is important for growth recovery upon nutrient replenishment. Here, TORC1 is found to regulate this process by directly targeting a conserved ribosome preservation factor.

  • TORC1 phosphorylates and inhibits Stm1 to prevent formation of dormant 80S ribosome under nutrient-sufficient conditions in yeast.
  • TORC1 inhibition by rapamycin or nitrogen starvation causes Stm1 binding to ribosomes.
  • Stm1-bound dormant, nontranslating 80S ribosomes are protected from proteasomal degradation.
  • mTORC1 phosphorylates and inhibits the mammalian Stm1 ortholog SERBP1.
  • SERBP1 is required for ribosome protection upon mTORC1 inhibition in human cells, suggesting conserved regulation.

Abstract
Target of rapamycin complex 1 (TORC1) promotes biogenesis and inhibits the degradation of ribosomes in response to nutrient availability. To ensure a basal supply of ribosomes, cells are known to preserve a small pool of dormant ribosomes under nutrient-limited conditions. However, the regulation of these dormant ribosomes is poorly characterized. Here, we show that upon inhibition of yeast TORC1 by rapamycin or nitrogen starvation, the ribosome preservation factor Stm1 mediates the formation of nontranslating, dormant 80S ribosomes. Furthermore, Stm1-bound 80S ribosomes are protected from proteasomal degradation. Upon nutrient replenishment, TORC1 directly phosphorylates and inhibits Stm1 to reactivate translation. Finally, we find that SERBP1, a mammalian ortholog of Stm1, is likewise required for the formation of dormant 80S ribosomes upon mTORC1 inhibition in mammalian cells. These data suggest that TORC1 regulates ribosomal dormancy in an evolutionarily conserved manner by directly targeting a ribosome preservation factor.

Read the Publication in the EMBO Journal (Open Access)

Website Hall lab

Abstract, figure and title from Shetty et al. (2023) EMBO J published under a CC BY-NC-ND 4.0 license.