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MBC in Press, published online ahead of print June 18, 2008
Mol. Biol. Cell 10.1091/mbc.E08-02-0184

A more recent version of this article appeared on September 1, 2008 Originally published as MBC in Press, 10.1091/mbc.E08-02-0184 on July 2, 2008
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Submitted on February 20, 2008
Accepted on June 6, 2008

Telomerase Reverse Transcriptase Is Required for the Localization of Telomerase RNA to Cajal Bodies and Telomerese in Human Cancer Cells

Rebecca L. Tomlinson,* Eladio B. Abreu,* Tania Ziegler,* Hinh Ly,{dagger} Christopher M. Counter,{ddagger} Rebecca M. Terns,* and Michael P. Terns*

*Departments of Biochemistry and Molecular Biology, and Genetics, University of Georgia, Athens, GA 30602; {dagger}Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30332; {ddagger}Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710

Monitoring Editor: A. Gregory Matera

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 upon the assembly of the enzyme.


Address correspondence to: Michael P. Terns (mterns{at}bmb.uga.edu)




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