The target of rapamycin complex 1 (TORC1) is an essential regulator of eukaryotic cell growth that responds to growth factors, energy levels, and amino acids. The mechanisms through which the preeminent amino acid leucine signals to the TORC1-regulatory Rag GTPases, which activate TORC1 within the yeast EGO complex (EGOC) or the structurally related mammalian Rag-Ragulator complex, remain elusive. We find that the leucyl-tRNA synthetase (LeuRS) Cdc60 interacts with the Rag GTPase Gtr1 of the EGOC in a leucine-dependent manner. This interaction is necessary and sufficient to mediate leucine signaling to TORC1 and is disrupted by the engagement of Cdc60 in editing mischarged tRNA Leu. Thus, the EGOC-TORC1 signaling module samples, via the LeuRS-intrinsic editing domain, the fidelity of tRNA Leu aminoacylation as a proxy for leucine availability. © 2012 Elsevier Inc.
Bonfils, G., Jaquenoud, M., Bontron, S., Ostrowicz, C., Ungermann, C., & De Virgilio, C. (2012). Leucyl-tRNA Synthetase Controls TORC1 via the EGO Complex. Molecular Cell, 46(1), 105–110. https://doi.org/10.1016/j.molcel.2012.02.009