Telomerase is a ribonucleoprotein enzyme that extends and stabilizes the ends of chromosomes, allowing cells to continuously divide without loss of genetic material. In humans, telomerase has been implicated in cellular immortalization and cancer progression. Therefore, attaining a precise understanding of telomerase structure and function is critical to illuminating the pathway of molecular events that leads to cancer, and to developing more effective cancer therapies. The long-term objective of this research proposal is to elucidate properties of human telomerase that induce cellular lifespan extension. The proposed research will address the contribution to in vivo telomerase function by the pseudoknot P3 region in the human telomerase RNA subunit (hTER). Cellular growth effects of P3 mutations will be examined, and the importance of P3-induced hTER dimerization will be investigated in vivo by expressing compensatory P3 mutations in trans and in vitro by RNA crosslinking experiments. Furthermore, this research seeks to identify novel telomerase-interacting proteins that mediate telomerase function in human cells.
