Reciprocal regulation of TORC signaling and tRNA modifications by Elongator enforces nutrient-dependent cell fate
Reciprocal regulation of TORC signaling and tRNA modifications by Elongator enforces nutrient-dependent cell fate
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DOI：
10.1126/sciadv.aav0184
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发表时间：
2019-06-01
期刊：
影响因子：
13.6
通讯作者：
Hermand, Damien
中科院分区：
文献类型：
--
作者：
Candiracci, Julie;Migeot, Valerie;Hermand, Damien
营养物质的供应对细胞的命运有着深远的影响。在氮饥饿时，野生型裂变酵母细胞将细胞生长与细胞分裂解偶联，以产生能够进行性分化的小的圆形细胞。TORC 1（TOR复合物1）和TORC 2复合物对细胞生长和细胞分化发挥相反的控制作用，但对它们的活性如何协调知之甚少。我们发现，通过延长子的转移RNA（tRNA）修饰通过促进TORC2的关键组分和TORC1的阻遏物的翻译对这种调节至关重要。我们进一步确定了TORC 2途径作为Elongator的激活剂，通过下调Elongator的Gsk 3（糖原合成酶激酶3）依赖性抑制磷酸化。因此，反馈控制在TOR复合物（TORC）信号传导和延伸子的tRNA修饰之间起作用，以在细胞分化之前强制推进有丝分裂。
Nutrient availability has a profound impact on cell fate. Upon nitrogen starvation, wild-type fission yeast cells uncouple cell growth from cell division to generate small, round-shaped cells that are competent for sexual differentiation. The TORC1 (TOR complex 1) and TORC2 complexes exert opposite controls on cell growth and cell differentiation, but little is known about how their activity is coordinated. We show that transfer RNA (tRNA) modifications by Elongator are critical for this regulation by promoting the translation of both key components of TORC2 and repressors of TORC1. We further identified the TORC2 pathway as an activator of Elongator by down-regulating a Gsk3 (glycogen synthase kinase 3)-dependent inhibitory phosphorylation of Elongator. Therefore, a feedback control is operating between TOR complex (TORC) signaling and tRNA modification by Elongator to enforce the advancement of mitosis that precedes cell differentiation.