Structure and function of the telomerase complex. (A) TERT enzymatically adds TTAGGG nucleotide repeats to the 3′ end of telomere's leading strand using TERC as a template. Other proteins (dyskerin, NOP10, NHP2, and GAR) also bind to TERC and stabilize the complex. (B) Linear structure of TERT, which is highly conserved among eukaryotes and consists of the central reverse transcriptase (RT) motifs (1, 2, A, B, C, D, and E), a large N-terminal region, and a short C-terminal region, all necessary for telomerase enzymatic function. The N-terminal region comprises a telomerase-essential N-terminal domain (TEN), the CP, and the QFP domains, required for RNA interaction, and a telomerase-specific T motif. The C-terminal region contains 4 conserved domains (E-I to E-IV). (C) Secondary structure of human TERC, which contains 7 conserved regions (CRs), a pseudoknot important for interaction with TERT (CR2/CR3), and a template used by TERT for telomere elongation (CR1). TERC also encloses a small nucleolar H/ACA motif; box H/ACA refers to a tail region of small nucleolar RNAs (snoRNAs) carrying a conserved H motif (AnAnnA) and consensus ACA triplet positioned 3 nucleotides before the 3′ end of the RNA that characterize a major snoRNA family involved in pseudouridylation of pre-rRNAs.²⁸  TERC binds to other proteins, such as dyskerin, GAR, NHP2, and NOP10, through box H/ACA.