Leucyl-tRNA Synthetase Controls TORC1 via the EGO Complex

SummaryThe 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 tRNALeu. Thus, the EGOC-TORC1 signaling module samples, via the LeuRS-intrinsic editing domain, the fidelity of tRNALeu aminoacylation as a proxy for leucine availability.

► Leucyl-tRNA synthetase Cdc60 interacts with Gtr1 in a leucine-dependent manner
► This interaction is necessary and sufficient to mediate leucine signaling to TORC1
► Engagement of Cdc60 in amino acid-editing disrupts the Cdc60-Gtr1 interaction
► TORC1 samples tRNALeu aminoacylation fidelity as a proxy for leucine availability