Telomerase structure and evolution

The integrity of eukaryotic genomes is derived in part from telomeres, the nucleoprotein caps on chromosome ends. Telomeric DNA is maintained by the telomerase reverse transcriptase, a ribonucleoprotein complex that continually replenishes telomeric DNA using a catalyst TERT and an integral long noncoding RNA, TR, as a template.  Mis-regulation of telomerase is linked to stem cell disease and tumorigenesis in humans. The critical function of telomeres was demonstrated in plants 80 years ago by the pioneering work of Barbara McClintock. A half century later, our lab developed Arabidopsis thaliana as a powerful comparative model organism for elucidating fundamental aspects of telomere biology. The predominant structure models for telomerase derive human and Tetrahymena telomerases. We recently identified TR from A. thaliana and working with collaborators from Arizona State University developed a robust secondary structure model for plant TR that provided an evolutionary bridge for the highly divergent TR molecules studied to date. TERT and TR are common to all telomerases, but the accessory subunits of the enzyme complex are unique to each particle. A current focus in the lab is comprehensive identification of telomerase-associated factors and acquisition of a 3D structure for plant telomerases to uncover both novel mechanisms and unifying principles for this essential enzyme. 

Plant TRs maintain a conserved secondary structure. Using a combination of phylogenetic analysis and RNA structural mapping, we developed a robust secondary structure model for A. thaliana (right) and more than 80 other plant species. Plant TR maintains conserved RNA motifs including template-pseudoknot and 3’ stem-loop. Close inspection of the pseudoknot indicates that plant TR is the missing link for an evolutionary pathway that unites divergent TR structures from ciliated protozoa to humans (left). See PNAS116(49): 24542-24550.

Song, J., D. Logeswaran, C. Castillo-Gonzalez, Y. Li, S. Bose, B. B. Aklilu, Z. Ma, A. Polkhovskiy, J. J. Chen and D. E. Shippen (2019). "The conserved structure of plant telomerase RNA provides the missing link for an evolutionary pathway from ciliates to humans." Proc. Natl. Acad. Sci. USA 116(49): 24542-24550.