Single-Molecule FRET Reveals the Folding Dynamics of the Human Telomerase RNA Pseudoknot Domain†

Telomerase catalyzed synthesis of telomere DNA provides the foundation for DNA-protein structures called telomeres. Telomeres are required to evade DNA processing which may result in nucleolytic degradation and fusion of linear chromosomes. Human telomerase contains a protein reverse transcriptase (hTERT), telomerase RNA (hTR), and several additional proteins.[1] hTR provides the template sequence for hTERT during a novel reverse transcription reaction that produces short telomere DNA repeat sequences.[2] Additionally, hTR provides a flexible scaffold for the assembly and function of telomerase associated proteins[3] and has recently been suggested to contribute to enzyme catalysis.[4] Many pathogenic mutations have been mapped to hTR;[5] however the precise mechanisms of these mutations remain unclear.