Book of Abstracts: Albany 2003
June 17-21 2003
Structural and Conformational Properties of the Functionally Essential Domains in Tetrahymena thermophilus Telomerase RNA
Telomerase is a ribonucleoprotein, which is responsible for the replication of telomere DNA found at the physical ends of chromosomes. These termini of telomeric DNA cannot be fully replicated by conventional replication machinery, and consequently, chromosomes shorten at each cell division. Telomerase activity is generally undetectable is somatic cells, and high level of telomerase activity are only found in proliferating germ cells and cancer cells. 80-90% of diverse human tumors show telomerase activity, while adjacent healthy tissues are typically negative for telomerase activity (1, 2). This makes telomerase an attractive target for chemotherapies and telomerase activity a potential diagnostic for tumor-genesis (2).
Here, we investigate the relationship between conformational properties of phylogenetically conserved domains of telomerase RNA (TR) and their function in Tetrahymena thermophila. The results of NMR structure analysis of stem IV, loop IV, and pseudoknot domains of Tetrahymena TR will be presented . We have used principal order matrix analysis of residual dipolar couplings and molecular modeling in order to detect and quantify the inter-domain motion and the structural bending in stem IV. Using 1H and 13C chemical shift changes and UV melting we have probed possible tertiary interactions between the loop IV and the pseudoknot domains. The results will be presented in terms of the proposed mechanism for the function of telomerase RNA, and they will be compared to corresponding conformational features in human telomerase RNA (3).
Department of Chemistry and Biochemistry, University of California Los Angeles,
P.O .Box 951569