TORC2 inactivation promotes heterochromatin formation in rDNA and prolongs viability of quiescent fission yeast cells.

Abstract

A large amount of the energy produced by glucose is consumed in the biogenesis of ribosomes, the cellular machinery for protein synthesis. Recent studies suggest that a low-calorie diet and the suppression of ribosome biogenesis can extend lifespan. However, the molecular mechanisms underlying these phenomena remain elusive. Here, we demonstrate that TORC2 (TOR complex 2) promotes ribosomal RNA (rRNA) transcription by facilitating the association of Paf1C (RNA polymerase II-associated factor 1 complex) with the rDNA region. Under glucose starvation, inactivation of the TORC2-Gad8 pathway leads to the dissociation of Paf1C from rDNA, thereby promoting heterochromatin formation and transcriptional repression. This mechanism is distinct from TORC1-mediated gene regulation of rDNA. Additionally, simultaneous inactivation of the redundant TORC1 and TORC2 pathways in nutrient-rich conditions leads to robust rDNA heterochromatin formation and rRNA transcriptional suppression, which is associated with prolonged viability of quiescent cells. This extension of viability is attenuated by the disruption of the H3K9 methyltransferase Clr4. These results suggest that robust heterochromatin formation in the rDNA region may support sustained survival of quiescent cells.