Telomerase reverse transcriptase is required for the localization of telomerase RNA to cajal bodies and telomeres in human cancer cells

Telomere maintenance by telomerase is critical for the unlimited division potential of most human cancer cells. The two essential components of human telomerase, telomerase RNA (hTR) and telomerase reverse transcriptase (hTERT), are recruited from distinct subnuclear sites to telomeres during S phas...

Full description

Saved in:
Bibliographic Details
Published inMolecular biology of the cell Vol. 19; no. 9; pp. 3793 - 3800
Main Authors Tomlinson, Rebecca L, Abreu, Eladio B, Ziegler, Tania, Ly, Hinh, Counter, Christopher M, Terns, Rebecca M, Terns, Michael P
Format Journal Article
LanguageEnglish
Published United States The American Society for Cell Biology 01.09.2008
SeriesAn InCytes from MBC Selection
Subjects
Antigens, Polyomavirus Transforming - metabolism
Bromodeoxyuridine - pharmacology
Cell Line, Tumor
Coiled Bodies - metabolism
Gene Expression Regulation, Neoplastic
HeLa Cells
Humans
In Situ Hybridization, Fluorescence
Microscopy, Fluorescence
RNA - metabolism
RNA, Long Noncoding
RNA, Untranslated
S Phase
Telomerase - metabolism
Telomere - metabolism
Online AccessGet full text

Cover

More Information
Summary:Telomere maintenance by telomerase is critical for the unlimited division potential of most human cancer cells. The two essential components of human telomerase, telomerase RNA (hTR) and telomerase reverse transcriptase (hTERT), are recruited from distinct subnuclear sites to telomeres during S phase. Throughout the remainder of the cell cycle hTR is found primarily in Cajal bodies. The localization of hTR to Cajal bodies and telomeres is specific to cancer cells where telomerase is active and is not observed in primary cells. Here we show that the trafficking of hTR to both telomeres and Cajal bodies depends on hTERT. RNA interference-mediated depletion of hTERT in cancer cells leads to loss of hTR from both Cajal bodies and telomeres without affecting hTR levels. In addition, expression of hTERT in telomerase-negative cells (including primary and ALT cancer cell lines) induces hTR to localize to both sites. Factors that did not stimulate hTR localization in our experiments include increased hTR RNA levels and Cajal body numbers, and expression of SV40 large T antigen and oncogenic Ras. Our findings suggest that the trafficking of telomerase to Cajal bodies and telomeres in cancer cells correlates with and depends on the assembly of the enzyme.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.E08-02-0184