Grant: Operating Grant

Cell division is triggered when a cell has reached a critical size, and attainment of this size is highly dependent on the overall protein translation rate. An important contributor to the translation rate is nuclear tRNA export, as evidenced by increased transcription of tRNA genes in cells lacking the tumor suppressor protein p53 or RB, and increased expression of the mammalian nuclear tRNA export receptor exportin-t (Xpo-t) in rapidly dividing cells (29). Nuclear tRNA export also plays an important role in cell cycle regulation in Saccharomyces cerevisiae, since cells arrest in G1 upon depletion of Utp8p, an essential intranuclear component of the nuclear tRNA export machinery, and by redistribution of the nuclear tRNA export receptor Los1p to the cytoplasm when the DNA is damaged. More recent studies have shown that nuclear import of tRNAs also plays an important role in nutrient-related regulation of cell growth, and to facilitate transport of the HIV-1 replication complexes into the nucleus of HeLa cells. Thus, tRNA trafficking between the nucleus and cytoplasm is of fundamental importance to cell biology, and disruption of this process is likely to have grave consequences on cell viability and ultimately survival of the organism. The goal of this research is to understand the mechanism of nuclear tRNA export in mammalian cells by identifying and characterizing the proteins associated with the process.