tRNA trafficking along the TOR pathway

3146 Cell Cycle Volume 9 Issue 16 Adaptation of metabolic activity to nutrient availability is among the most ancestral of cellular behaviors. Resource-intensive processes such as growth and protein synthesis are particularly tightly coupled to nutrient levels, ensuring that cells devote resources to these functions only under appropriate conditions. The target of rapamycin (TOR) protein kinase is an essential and conserved component of such regulation, and orchestrates a comprehensive set of cellular responses to nutrient levels. Under favorable conditions, TOR signaling promotes protein synthesis through upregulation of ribosome biogenesis and direct activation of the translation machinery. In response to nutrient withdrawal, reduction of TOR activity inhibits biosynthesis and causes activation of autophagy, in which cytoplasmic components are degraded in the lysosomal compartment. These responses promote cell survival during periods of starvation by reducing demand and generating an intracellular source of recycled nutrients. How the TOR pathway senses nutrient status is only partially understood. One upstream signal involves the Rag family of small GTPases, which regulate the association of TOR with the GTPase Rheb, a direct activator of TOR. The more proximal upstream steps in this pathway by which amino acid levels are assessed have remained elusive, with nutrient transporters, uncharged tRNAs, and intracellular levels of ATP or calcium each being proposed as potential mediators of the signal.1 tRNAs are essential intermediates of protein synthesis, translating the mRNA ribonucleotide code into polypeptide sequence. tRNAs synthesized in the nucleus are actively exported to the cytoplasm by specific transport factors. Recent studies in yeast and mammalian cells have also identified a retrograde pathway of tRNA import into the nucleus.2,3 Interestingly, the balance between nuclear and cytoplasmic pools of tRNA is regulated by nutrient availability, with starvation causing a rapid and reversible accumulation of tRNA in the nucleus. This response has been Cell Cycle News & Views