Telomerase RNA Accumulates in Cajal Bodies in Human Cancer Cells

Abstract

Telomerase synthesizes telomeric DNA repeats at the ends of eukaryotic chromosomes. The RNA component of the enzyme (hTR) provides the template for telomere synthesis, which is catalyzed by telomerase reverse transcriptase (hTERT). Little is known regarding the subcellular localization of hTR and hTERT and the pathway by which telomerase is assembled. Here we report the first glimpse of the detailed subcellular localization of endogenous hTR in human cells, which we obtained by fluorescence in situ hybridization (FISH). Our studies have revealed a distinctive hTR localization pattern in cancer cells. We have found that hTR accumulates within intranuclear foci called Cajal bodies in all typical tumor-derived cell lines examined (in which telomerase is active), but not in primary or ALT cells (where little or no hTERT is present). Accumulation of hTR in the Cajal bodies of primary cells is induced when hTERT is ectopically expressed. Moreover, we report that hTERT is also found in Cajal bodies. Our data suggest that Cajal bodies are involved in the assembly and/or function of human telomerase.

Single Cell Analysis of RNA-mediated Histone H3.3 Recruitment to a Cytomegalovirus Promoter-regulated Transcription Site

“…TERT, the protein subunit of telomerase, is reported to function as an RNA-dependent RNA polymerase (82). However, TERT is not expressed in the ALT-positive U2OS cell line (83,84), suggesting that it is not responsible for the AS transcription at the CMV promoter-regulated array.…”

Coilin: The first 25 years

“…Early experiments detected telomerase RNA in CBs, and CBs associate with telomerase during Sphase. [38][39][40][41][42] Interestingly, telomerase RNA localization to CBs seems to be humanspecific because telomerase RNA was not found in mouse CBs. 43 Telomerase RNA is retained in CBs via protein WRAP53, which binds the CAB box sequence found in telomerase RNA and many scaRNAs.…”

Physiological assembly and activity of human telomerase complexes

“…In situ hybridization studies suggest that for most of the cell cycle, the highest concentration of hTR is in Cajal bodies (Jády et al, 2004;Zhu et al, 2004). These intranuclear structures are sites of small nuclear RNP biogenesis and function (Handwerger and Gall, 2006).…”

“…For cell types in which hTR can be detected by in situ hybridization, the highest intranuclear concentration of hTR is in Cajal bodies (Jády et al, 2004;Zhu et al, 2004). A large fraction of hTR may be nucleoplasmic, perhaps too diffuse to detect by in situ hybridization.…”