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Telomerase stimulates ribosomal DNA transcription under hyperproliferative conditions

Author

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  • Omar Garcia Gonzalez

    (Clinic of Dermatology and Allergic Diseases, University Medical Center, Albert-Einstein-Allee 23, 89081 Ulm, Germany)

  • Robin Assfalg

    (Clinic of Dermatology and Allergic Diseases, University Medical Center, Albert-Einstein-Allee 23, 89081 Ulm, Germany)

  • Sylvia Koch

    (Clinic of Dermatology and Allergic Diseases, University Medical Center, Albert-Einstein-Allee 23, 89081 Ulm, Germany)

  • Adrian Schelling

    (Clinic of Dermatology and Allergic Diseases, University Medical Center, Albert-Einstein-Allee 23, 89081 Ulm, Germany)

  • Jitendra K. Meena

    (Leibniz Institute for Age Research, Fritz Lipmann Institute, Beutenbergstrasse 11)

  • Johann Kraus

    (Research Group Bioinformatics and Systems Biology, Ulm University)

  • Andre Lechel

    (University Medical Center, Albert-Einstein-Allee 23)

  • Sarah-Fee Katz

    (University Medical Center, Albert-Einstein-Allee 23)

  • Vladimir Benes

    (European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1)

  • Karin Scharffetter-Kochanek

    (Clinic of Dermatology and Allergic Diseases, University Medical Center, Albert-Einstein-Allee 23, 89081 Ulm, Germany)

  • Hans A. Kestler

    (Research Group Bioinformatics and Systems Biology, Ulm University)

  • Cagatay Günes

    (Leibniz Institute for Age Research, Fritz Lipmann Institute, Beutenbergstrasse 11)

  • Sebastian Iben

    (Clinic of Dermatology and Allergic Diseases, University Medical Center, Albert-Einstein-Allee 23, 89081 Ulm, 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.

Suggested Citation

  • Omar Garcia Gonzalez & Robin Assfalg & Sylvia Koch & Adrian Schelling & Jitendra K. Meena & Johann Kraus & Andre Lechel & Sarah-Fee Katz & Vladimir Benes & Karin Scharffetter-Kochanek & Hans A. Kestle, 2014. "Telomerase stimulates ribosomal DNA transcription under hyperproliferative conditions," Nature Communications, Nature, vol. 5(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5599
    DOI: 10.1038/ncomms5599
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