Telomerase stimulates ribosomal DNA transcription under hyperproliferative conditions

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. Kestler, Cagatay Günes (+1 others)
2014 Nature Communications  
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
more » ... nscription 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.
doi:10.1038/ncomms5599 pmid:25118183 fatcat:6qfgyqrfv5a5nd7ckj3vc7xf2e