TOR complex1 (TORC1), a master regulator of cell growth, is regulated by amino acids. Amino acids are fundamental nutrients, and 20 species of amino acids building proteins are not interchangeable with each other. Therefore, TORC1 should sense each amino acid individually. Mammalian mTORC1 is controlled by Rag GTPases and their regulators. However, Rag factors are dispensable for amino acid sensing by TORC1 in the budding yeast, suggesting an alternative mechanism of TORC1 regulation. Here, genetic investigation discovered the involvement of (aminoacyl-)tRNA ((aa-)tRNA) in TORC1 regulation. Biochemical TORC1 assay also showed that tRNA directly inhibits TORC1 kinase activity. Reducing cellular tRNA molecule desensitizes TORC1 inactivation by nitrogen starvation in vivo. Based on these results, I propose a model of the TORC1 regulatory mechanism in which free tRNA released from protein synthesis under amino acid starvation inhibits TORC1 activity. Therefore, TORC1 uses tRNA-mediated mechanism and Rag factors in parallel to sense intracellular amino acids.

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Kamada Y

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