Reciprocal regulation of TORC signaling and tRNA modifications by Elongator enforces nutrient-dependent cell fate

Nutrient availability has a profound impact on cell fate. Upon nitrogen starvation, wild-type fission yeast cells uncouple cell growthfrom 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 growthand cell differentiation, but little is known about how their activity is coordinated. We show that transfer RNA(tRNA) modifications by Elongatorare 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 Elongatorby down-regulating a Gsk3 ( glycogen synthasekinase 3)–dependent inhibitory phosphorylation of Elongator. Therefore, a feedback control is operating between TOR complex ( TORC) signaling and tRNA modification by Elongatorto enforce the advancement of mitosis that precedes cell differentiation.