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Molecular and Cellular Biology, June 1999, p. 3989-3997, Vol. 19, No. 6
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Both Transcriptional and Posttranscriptional Mechanisms Regulate Human Telomerase Template RNA Levels

Xiaoming Yi, Valerie M. Tesmer, Isabelle Savre-Train, Jerry W. Shay, and Woodring E. Wright*

Department of Cell Biology and Neuroscience, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75235-9039

Received 19 November 1998/Returned for modification 22 December 1998/Accepted 22 February 1999

The human telomerase RNA component (hTR) is present in normal somatic cells at lower levels than in cancer-derived cell lines. To understand the mechanisms regulating hTR levels in different cell types, we have compared the steady-state hTR levels in three groups of cells: (i) normal telomerase-negative human diploid cells; (ii) normal cells transfected with the human telomerase catalytic subunit, hTERT; and (iii) cells immortalized in vitro and cancer cells expressing their own endogenous hTERT. To account for the differences in steady-state hTR levels observed in these cell types, we compared the transcription rate and half-life of hTR in a subset of these cells. The half-life of hTR in telomerase-negative cells is about 5 days and is increased 1.6-fold in the presence of hTERT. The transcription rate of hTR is essentially unchanged in cells expressing exogenous hTERT, and the increased steady-state hTR level appears to be due to the increased half-life. However, the transcription rate of hTR is greatly increased in cells expressing endogenous hTERT, suggesting some overlap in transcriptional regulatory control. We conclude that the higher hTR level in cells expressing an endogenous telomerase can be a result of both increased transcription and a longer half-life and that the longer half-life might be partially a result of protection or stabilization by the telomerase catalytic subunit. The 4-week half-life of hTR in H1299 tumor cells is the longest half-life yet reported for any RNA.

* Corresponding author. Mailing address: Department of Cell Biology and Neuroscience, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, TX 75235-9039. Phone: (214) 648-2933. Fax: (214) 648-8694. E-mail: wright{at}utsw.swmed.edu.

Molecular and Cellular Biology, June 1999, p. 3989-3997, Vol. 19, No. 6
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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