title: Telomerase stimulates ribosomal DNA transcription under hyperproliferative conditions.
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.
authors.affiliation: Clinic of Dermatology and Allergic Diseases, University Medical Center, Albert-Einstein-Allee 23, 89081 Ulm, Germany.
authors.forename: Omar Garcia
authors.initials: OG
authors.lastname: Gonzalez
authors.affiliation: Clinic of Dermatology and Allergic Diseases, University Medical Center, Albert-Einstein-Allee 23, 89081 Ulm, Germany.
authors.forename: Robin
authors.initials: R
authors.lastname: Assfalg
authors.affiliation: Clinic of Dermatology and Allergic Diseases, University Medical Center, Albert-Einstein-Allee 23, 89081 Ulm, Germany.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Koch
authors.affiliation: Clinic of Dermatology and Allergic Diseases, University Medical Center, Albert-Einstein-Allee 23, 89081 Ulm, Germany.
authors.forename: Adrian
authors.initials: A
authors.lastname: Schelling
authors.affiliation: Leibniz Institute for Age Research, Fritz Lipmann Institute, Beutenbergstrasse 11, 07745 Jena, Germany.
authors.forename: Jitendra K
authors.initials: JK
authors.lastname: Meena
authors.affiliation: Research Group Bioinformatics and Systems Biology, Ulm University, 89069 Ulm, Germany.
authors.forename: Johann
authors.initials: J
authors.lastname: Kraus
authors.affiliation: Department of Internal Medicine I, University Medical Center, Albert-Einstein-Allee 23, 89081 Ulm, Germany.
authors.forename: Andre
authors.initials: A
authors.lastname: Lechel
authors.affiliation: Department of Internal Medicine I, University Medical Center, Albert-Einstein-Allee 23, 89081 Ulm, Germany.
authors.forename: Sarah-Fee
authors.initials: SF
authors.lastname: Katz
authors.affiliation: European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Benes
authors.affiliation: Clinic of Dermatology and Allergic Diseases, University Medical Center, Albert-Einstein-Allee 23, 89081 Ulm, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Scharffetter-Kochanek
authors.affiliation: Research Group Bioinformatics and Systems Biology, Ulm University, 89069 Ulm, Germany.
authors.forename: Hans A
authors.initials: HA
authors.lastname: Kestler
authors.affiliation: Leibniz Institute for Age Research, Fritz Lipmann Institute, Beutenbergstrasse 11, 07745 Jena, Germany.
authors.forename: Cagatay
authors.initials: C
authors.lastname: Günes
authors.affiliation: Clinic of Dermatology and Allergic Diseases, University Medical Center, Albert-Einstein-Allee 23, 89081 Ulm, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Iben
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology*; D015179:Colorectal Neoplasms / Q000473:pathology; D004275:DNA, Ribosomal / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000166:cytology; D008099:Liver / Q000166:cytology; D008115:Liver Regeneration / Q000235:genetics / Q000502:physiology; D008168:Lung / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058628:Myofibroblasts / Q000166:cytology; D011485:Protein Binding / Q000502:physiology; D012318:RNA Polymerase I / Q000235:genetics / Q000502:physiology*; D011817:Rabbits; D019098:Telomerase / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000235:genetics / Q000502:physiology*
chemical_list: D004275:DNA, Ribosomal; C509186:TERT protein, human; D019098:Telomerase; C509187:Tert protein, mouse; D012318:RNA Polymerase I