Telomerase Efficiently Elongates Highly Transcribing Telomeres in Human Cancer Cells

RNA polymerase II transcribes the physical ends of linear eukaryotic chromosomes into a variety of long non-coding RNA molecules including telomeric repeat-containing RNA (TERRA). Since TERRA discovery, advances have been made in the characterization of TERRA biogenesis and regulation; on the contra...

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Main Authors:	Farnung, Benjamin O., Brun, Catherine M., Arora, Rajika, Lorenzi, Luca E., Azzalin, Claus M.
Format:	Online
Language:	English
Published:	Public Library of Science 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3338753/

id	pubmed-3338753
recordtype	oai_dc
spelling	pubmed-33387532012-05-03 Telomerase Efficiently Elongates Highly Transcribing Telomeres in Human Cancer Cells Farnung, Benjamin O. Brun, Catherine M. Arora, Rajika Lorenzi, Luca E. Azzalin, Claus M. Research Article RNA polymerase II transcribes the physical ends of linear eukaryotic chromosomes into a variety of long non-coding RNA molecules including telomeric repeat-containing RNA (TERRA). Since TERRA discovery, advances have been made in the characterization of TERRA biogenesis and regulation; on the contrary its associated functions remain elusive. Most of the biological roles so far proposed for TERRA are indeed based on in vitro experiments carried out using short TERRA-like RNA oligonucleotides. In particular, it has been suggested that TERRA inhibits telomerase activity. We have exploited two alternative cellular systems to test whether TERRA and/or telomere transcription influence telomerase-mediated telomere elongation in human cancer cells. In cells lacking the two DNA methyltransferases DNMT1 and DNMT3b, TERRA transcription and steady-state levels are greatly increased while telomerase is able to elongate telomeres normally. Similarly, telomerase can efficiently elongate transgenic inducible telomeres whose transcription has been experimentally augmented. Our data challenge the current hypothesis that TERRA functions as a general inhibitor of telomerase and suggest that telomere length homeostasis is maintained independently of TERRA and telomere transcription. Public Library of Science 2012-04-27 /pmc/articles/PMC3338753/ /pubmed/22558207 http://dx.doi.org/10.1371/journal.pone.0035714 Text en Farnung et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Farnung, Benjamin O. Brun, Catherine M. Arora, Rajika Lorenzi, Luca E. Azzalin, Claus M.
spellingShingle	Farnung, Benjamin O. Brun, Catherine M. Arora, Rajika Lorenzi, Luca E. Azzalin, Claus M. Telomerase Efficiently Elongates Highly Transcribing Telomeres in Human Cancer Cells
author_facet	Farnung, Benjamin O. Brun, Catherine M. Arora, Rajika Lorenzi, Luca E. Azzalin, Claus M.
author_sort	Farnung, Benjamin O.
title	Telomerase Efficiently Elongates Highly Transcribing Telomeres in Human Cancer Cells
title_short	Telomerase Efficiently Elongates Highly Transcribing Telomeres in Human Cancer Cells
title_full	Telomerase Efficiently Elongates Highly Transcribing Telomeres in Human Cancer Cells
title_fullStr	Telomerase Efficiently Elongates Highly Transcribing Telomeres in Human Cancer Cells
title_full_unstemmed	Telomerase Efficiently Elongates Highly Transcribing Telomeres in Human Cancer Cells
title_sort	telomerase efficiently elongates highly transcribing telomeres in human cancer cells
description	RNA polymerase II transcribes the physical ends of linear eukaryotic chromosomes into a variety of long non-coding RNA molecules including telomeric repeat-containing RNA (TERRA). Since TERRA discovery, advances have been made in the characterization of TERRA biogenesis and regulation; on the contrary its associated functions remain elusive. Most of the biological roles so far proposed for TERRA are indeed based on in vitro experiments carried out using short TERRA-like RNA oligonucleotides. In particular, it has been suggested that TERRA inhibits telomerase activity. We have exploited two alternative cellular systems to test whether TERRA and/or telomere transcription influence telomerase-mediated telomere elongation in human cancer cells. In cells lacking the two DNA methyltransferases DNMT1 and DNMT3b, TERRA transcription and steady-state levels are greatly increased while telomerase is able to elongate telomeres normally. Similarly, telomerase can efficiently elongate transgenic inducible telomeres whose transcription has been experimentally augmented. Our data challenge the current hypothesis that TERRA functions as a general inhibitor of telomerase and suggest that telomere length homeostasis is maintained independently of TERRA and telomere transcription.
publisher	Public Library of Science
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3338753/
_version_	1611525483424382976

Telomerase Efficiently Elongates Highly Transcribing Telomeres in Human Cancer Cells

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