Transcription regulates telomere dynamics in human cancer cells.

RNA
Rajika AroraClaus M Azzalin

Abstract

Telomeres are nucleoprotein structures capping the physical ends of linear eukaryotic chromosomes. Although largely heterochromatic, telomeres are transcribed into telomeric repeat-containing RNA (TERRA) molecules by RNA polymerase II. The functions associated with telomere transcription and TERRA remain ill defined. Here we show that the transcriptional activity of human telomeres directly regulates their movement during interphase. We find that chemical inhibition of global transcription dampens telomere motion, while global stimulation promotes it. Likewise, when DNA methyltransferase enzymes are deleted to augment telomere transcription, we observe increased telomere movement. Finally, using a cell line engineered with a unique transcriptionally inducible telomere, we show that transcription of one specific telomere stimulates only its own dynamics without overtly affecting its stability or its length. We reveal a new and unforeseen function for telomere transcription as a regulator of telomere motion, and speculate on the intriguing possibility that transcription-dependent telomere motion sustains the maintenance of functional and dysfunctional telomeres.

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Citations

Sep 4, 2014·Nature Communications·Isabel López de SilanesMaria A Blasco
Oct 22, 2014·Nature Communications·Rajika AroraClaus M Azzalin
Jun 26, 2012·Trends in Biochemical Sciences·J Arturo Londoño-Vallejo, Raymund J Wellinger
Nov 4, 2015·Chromosoma·Rita Reig-ViaderAurora Ruiz-Herrera
May 24, 2012·RNA Biology·André MaicherBrian Luke
Dec 4, 2012·Biophysical Journal·Krzysztof BurneckiAleksander Weron
Jul 6, 2014·Fertility and Sterility·Rita Reig-ViaderAurora Ruiz-Herrera
Sep 27, 2014·Trends in Cell Biology·Claus M Azzalin, Joachim Lingner
Oct 20, 2017·Genome Biology and Evolution·Matheus Sanitá Lima, David Roy Smith
May 8, 2016·EMBO Reports·Martin MoravecClaus M Azzalin
Dec 19, 2017·Chromosoma·Mathieu Tardat, Jérôme Déjardin
Jan 10, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Natalia M GalignianaGraciela Piwien-Pilipuk
Jun 12, 2021·Nature Communications·Jekaterina VohhodinaDavid M Livingston

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