a, Interactions between the RT and CTE domains of TERT and the substrate–template duplex. The RT domain is divided into two subdomains, the palm (green) and fingers (orange), that are commonly observed in retroviral reverse transcriptases. The CTE (cyan) is the putative thumb. The IFD insertion that is missing in the Tribolium TERT is indicated. b, Region of the cryo-EM reconstruction shown in a. Unassigned density close to the IFD insertion is highlighted in magenta. c, Cryo-EM density of the TEN domain in the same view as that in Fig. 4b. Connecting density is observed between the template region and the P2a.1 stem. d, Map of the CR4/5 three-way junction (wheat) and the nearby TERT domains highlighting the position of the P6.1 loop near the interface of the CTE (cyan) and TRBD (blue) domains of TERT. This loop was not ordered in medaka CR4/5 bound to the TRBD alone33. e, Comparison of the Tribolium (left) and medaka (right) TRBD with the medaka CR4/5 domain of hTR13,33. Extensions of the medaka TRBD that did not fit the map were truncated for visualization. f, Cryo-EM map with H/ACA components fitted. g, h, Detailed views of regions boxed in f show TCAB1 interactions with dyskerin, GAR1 and the P8 stem-loop (g), and interactions between the two dyskerin molecules (h), where a cluster of DC mutations are found (Fig. 5d). i, Comparison of the human and Tetrahymena TERT superposed on the RT domain. Domains of human TERT are coloured as in Fig. 1a, while Tetrahymena TERT is coloured grey. The bound human and Tetrahymena templates are coloured dark and light red, respectively. j, Comparison of human and Tetrahymena19 catalytic cores fitted into the corresponding cryo-EM maps. Domains of TERT were coloured as in Fig. 1a and TER is coloured yellow. We used the catalytic core and H/ACA lobe densities resulting from our focused classification/refinement for the human telomerase and the overall 9.4 Å Tetrahymena telomerase map (EMD-6442).