Telomerase activation. One step on the road to cancer?

Ever since the discovery that telomeres are short in cancer cells and telomerase is activated in immortal cells, telomerase has been an oncogene wannabe. Oncogenes have been the glamour genes of molecular biology for 20 years, garnering flashy headlines and name recognition. More recently, tumor-suppressor genes have joined oncogenes on center stage. Recent evidence has shown that MYC upregulates the catalytic subunit of telomerase, TERT, and that TERT cooperates with HPV E7 in cell immortalization. This evidence now supports the placement of telomerase among the cancer gene elite.     

A miniature yeast telomerase RNA functions in vivo and reconstitutes activity in vitro

The ribonucleoprotein enzyme telomerase synthesizes DNA at the ends of chromosomes. Although the telomerase catalytic protein subunit (TERT) is well conserved, the RNA component is rapidly evolving in both size and sequence. Here, we reduce the 1,157-nucleotide (nt) Saccharomyces cerevisiae TLC1 RNA to a size smaller than the 451-nt human RNA while retaining function in vivo. We conclude that long protein-binding arms are not essential for the RNA to serve its scaffolding function. Although viable, cells expressing Mini-T have shortened telomeres and reduced fitness as compared to wild-type cells, suggesting why the larger RNA has evolved. Previous attempts to reconstitute telomerase activity in vitro using TLC1 and yeast TERT (Est2p) have been unsuccessful. We find that substitution of Mini-T for wild-type TLC1 in a reconstituted system yields robust activity, allowing the contributions of individual yeast telomerase components to be directly assessed.