Abstract :
Homo sapiens telomerase RNA (hTR).
Human telomerase RNA was cloned by Feng et al. (1995). By in vitro and in vivo mapping experiments, Antal et al. (2002) showed that its 3' terminal domain folds into to a box H/ACA snoRNA-like "hairpin-hinge-hairpin-tail" structure, as previously predicted by Mitchell, Cheng and Collins (1999) and Chen, Blasco and Greider (2000). In agreement, RNP proteins associated with box H/ACA snoRNAs, including the pseudouridine synthase dyskerin, are also integral components of the human telomerase RNP (Mitchell, Wood and Collins, 1999; Filipowicz and Pogacic, 2002). The H/ACA domain of hTR is essential for both in vivo function and accumulation of telomerase (Fu and Collins, 2003). The autosomal dominant form of dyskeratosis congenita, an inherited skin and bone marrow failure syndrome, is due to mutations in hTR gene (Vulliamy et al. ,2001).
FISH experiments showed that hTR accumulates in Cajal bodies of cancer cells. Accordingly, the conserved CR7 region in the second hairpin of the H/ACA domain of hTR contains a Cajal body-specific localization signal previously recognized in small Cajal body-specific RNAs (scaRNAs) (Richard et al. 2003). The NMR structure of the CR7/CAB box was determined by Theimer et al. (2007).
