A structurally conserved human and Tetrahymena telomerase catalytic core

Significance Among reverse transcriptases, telomerase reverse transcriptase (TERT) has the unique ability to replenish DNA repeats at chromosome ends by repetitively using its integral RNA template. TERT shares a variety of common features with other reverse transcriptases as well as telomerase-specific motifs/domains. Among them, TEN and TRAP are not obviously present in all annotated TERT sequences, yet they form a complex in Tetrahymena telomerase that is essential for telomerase’ distinctive activities. Using bioinformatic and structural analysis we show that TEN and TRAP have coevolved and propose that they are defining features of TERT. We present a model for human telomerase that fits into the published cryoelectron microscopy map that will facilitate studies of mechanism, recruitment, and mutations linked to disease.