Cash, Darian

Darian is a first year trainee and is in the Department of Chemistry and Biochemistry. His research mentor is Dr. Juli Feigon. He received a B.S. degree in 2002 from U of Maryland.

Mentor: Dr. Juli Feigon

Research project:

Telomerase is a large ribonucleoprotein complex that replicates the 3' ends of linear chromosomes using an integral RNA template. Telomerase has been the focus of intense study due to its high level of activity in the majority (90%) of cancer cell lines and because of the correlation between telomere length and aging. The telomerase holoenzyme contains two components that are essential for catalytic activity, a reverse transcriptase (TERT) and a multi-domain RNA (TR). Aside from the template, other regions of the large telomerase RNA are also important for function, including the template-adjacent pseudoknot domain. NMR spectroscopy has been used to elucidate the solution structure of the pseudoknot domain of Kluyveromyces lactis yeast telomerase RNA. Similar to the human telomerase RNA pseudoknot, the structure reveals that the loops interact with the stems of the pseudoknot to form an extended triple helix which is essential for catalytic activity. The two structures have many things in common but there are a number of distinct differences between them as well, such as different arrangements of base triples around the junction, types of base triples and helical bends. While the vertebrate and yeast telomerase RNAs are highly divergent in size and sequence, comparison of the three-dimensional structures of the two pseudoknots shows that despite their differences they retain conserved structural elements in the critical core domain giving insight into the correlation between telomerase RNA structure and function.