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Nat Commun. 2014 Aug 13;5:4599. doi: 10.1038/ncomms5599.

Telomerase stimulates ribosomal DNA transcription under hyperproliferative conditions.

Author information

1
Clinic of Dermatology and Allergic Diseases, University Medical Center, Albert-Einstein-Allee 23, 89081 Ulm, Germany.
2
Leibniz Institute for Age Research, Fritz Lipmann Institute, Beutenbergstrasse 11, 07745 Jena, Germany.
3
Research Group Bioinformatics and Systems Biology, Ulm University, 89069 Ulm, Germany.
4
Department of Internal Medicine I, University Medical Center, Albert-Einstein-Allee 23, 89081 Ulm, Germany.
5
European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany.

Abstract

In addition to performing its canonical function, Telomerase Reverse Transcriptase (TERT) has been shown to participate in cellular processes independent of telomerase activity. Furthermore, although TERT mainly localizes to Cajal bodies, it is also present within the nucleolus. Because the nucleolus is the site of rDNA transcription, we investigated the possible role of telomerase in regulating RNA polymerase I (Pol I). Here we show that TERT binds to rDNA and stimulates transcription by Pol I during liver regeneration and Ras-induced hyperproliferation. Moreover, the inhibition of telomerase activity by TERT- or TERC-specific RNA interference, the overexpression of dominant-negative-TERT, and the application of the telomerase inhibitor imetelstat reduce Pol I transcription and the growth of tumour cells. In vitro, telomerase can stimulate the formation of the transcription initiation complex. Our results demonstrate how non-canonical features of telomerase may direct Pol I transcription in oncogenic and regenerative hyperproliferation.

PMID:
25118183
DOI:
10.1038/ncomms5599
[Indexed for MEDLINE]

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