Structural basis for protein-RNA recognition in telomerase

Arizona Sate University scientists take steps to unlock the secrets to the fountain of youth.

ASU scientists, together with collaborators from the Chinese Academy of Sciences in Shanghai, have published today, in Nature Structural and Molecular Biology, a first of its kind atomic level look at the enzyme telomerase that may unlock the secrets to the fountain of youth.

Telomeres and the enzyme telomerase have been in the medical news a lot recently due to their connection with aging and cancer. Telomeres are found at the ends of our chromosomes and are stretches of DNA which protect our genetic data, make it possible for cells to divide, and hold some secrets as to how we age –and also how we get cancer.

An analogy can be drawn between telomeres at the end of chromosomes and the plastic tips on shoelaces: the telomeres keep chromosome ends from fraying and sticking to each other, which would destroy or scramble our genetic information.

Each time one of our cells divides its telomeres get shorter. When they get too short, the cell can no longer divide and it becomes inactive or dies. This shortening process is associated with aging, cancer and a higher risk of death. The initial telomere lengths may differ between individuals. Clearly, size matters!

Caption: This image depicts telomeres on a chromosome and shows the different components required for telomerase activity as researched by professor Julian Chen of Arizona State University and published on 05/04/14 in Nature Structural and Molecular Biology. Credit: Joshua Podlevsky. Usage Restrictions: None

"Telomerase is crucial for telomere maintenance and genome integrity," explains Julian Chen, professor of chemistry and biochemistry at ASU and one of the project's senior authors. "Mutations that disrupt telomerase function have been linked to numerous human diseases that arise from telomere shortening and genome instability."

Chen continues that, "Despite the strong medical applications, the mechanism for telomerase holoenzyme (the most important unit of the telomerase complex) assembly remains poorly understood. We are particularly excited about this research because it provides, for the first time, an atomic level description of the protein-RNA interaction in the vertebrate telomerase complex."

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The other senior author on the project is professor Ming Lei who has recently relocated from the University of Michigan to Shanghai, China to lead a new National Center for Protein Science (affiliated with the Chinese Academy of Sciences).

The Department of Chemistry and Biochemistry at ASU, in the College of Liberal Arts and Sciences, ranks 6th worldwide for research impact (gauged by the average cites per paper across the department for the decade ending in the 2011 International Year of Chemistry) and in the top eight nationally for research publications in Science and Nature. The department's strong record in interdisciplinary research is also evidenced by its 31st national ranking by the NSF in total and federally financed higher education R&D expenditures in chemistry.

This work was supported by grants from the US National Institutes of Health (RO1GM094450 to J.J.-L.C.), Ministry of Science and Technology of China (2013CB910400 to M.L.), and the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB08010201 to M.L.).

Contact: Jenny Green jenny.green@asu.edu 480-965-1430 Arizona State University