Kusama Kino, Suzuki Yuta, Kurita Ena, Kawarasaki Tomoyuki, Obara Keisuke, Okumura Fumihiko, Kamura Takumi, Nakatsukasa Kunio
Graduate School of Science, Nagoya City University, Yamanohata 1, Mizuho-cho, Mizuho-ku, Nagoya, Aichi, 467-8501, Japan.
Division of Biological Sciences, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8602, Japan.
iScience. 2022 Feb 26;25(3):103986. doi: 10.1016/j.isci.2022.103986. eCollection 2022 Mar 18.
Ribosome biogenesis (Ribi) is a complex and energy-consuming process, and should therefore be repressed under nutrient-limited conditions to minimize unnecessary cellular energy consumption. In yeast, the transcriptional repressors Dot6 and Tod6 are phosphorylated and inactivated by the TORC1 pathway under nutrient-rich conditions, but are activated and repress ∼200 Ribi genes under nutrient-limited conditions. However, we show that in the presence of rapamycin or under nitrogen starvation conditions, Dot6 and Tod6 were readily degraded by the proteasome in a SCF and Tom1 ubiquitin ligase-dependent manner, respectively. Moreover, promiscuous accumulation of Dot6 and Tod6 excessively repressed Ribi gene expression as well as translation activity and caused a growth defect in the presence of rapamycin. Thus, we propose that degradation of Dot6 and Tod6 is a novel mechanism to ensure an appropriate level of Ribi gene expression and thereby fine-tune the repression of Ribi and translation activity for cell survival under nutrient-limited conditions.
核糖体生物发生（Ribi）是一个复杂且耗能的过程，因此在营养受限条件下应受到抑制，以尽量减少不必要的细胞能量消耗。在酵母中，转录抑制因子Dot6和Tod6在营养丰富的条件下被TORC1途径磷酸化并失活，但在营养受限的条件下被激活并抑制约200个Ribi基因。然而，我们发现，在雷帕霉素存在或氮饥饿条件下，Dot6和Tod6分别被蛋白酶体以依赖SCF和Tom1泛素连接酶的方式迅速降解。此外，Dot6和Tod6的杂乱积累过度抑制了Ribi基因的表达以及翻译活性，并在雷帕霉素存在的情况下导致生长缺陷。因此，我们提出，Dot6和Tod6的降解是一种新机制，可确保Ribi基因表达达到适当水平，从而在营养受限条件下微调对Ribi和翻译活性的抑制，以维持细胞存活。
