Human telomerase contains two cooperating telomerase RNA molecules

Telomerase uses a short stretch of its intrinsic RNA molecule as template f or telomere repeat synthesis. Reverse transcription of the RNA template is catalyzed by the telomerase reverse transcriptase (TERT) protein subunit, W e demonstrate that human telomerase reconstituted from recombinant TERT and telomerase RNA runs as a dimer on a gel filtration column and that it cont ains two telomerase RNA molecules. Significantly, a telomerase heterodimer reconstituted from wild-type and mutant telomerase RNA is barely active whe n compared with the wildtype homodimer. We conclude that the telomerase RNA templates in the active enzyme are interdependent and functionally coopera te with each other, We discuss models that may explain the biological and e nzymatic roles of telomerase dimerization.