telomerase efficiently elongates highly transcribing telomeres in human cancer cells端粒酶有效地拉长高度抄录在人类癌症细胞端粒.pdf
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Telomerase Efficiently Elongates Highly Transcribing
Telomeres in Human Cancer Cells
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Benjamin O. Farnung , Catherine M. Brun , Rajika Arora, Luca E. Lorenzi, Claus M. Azzalin*
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Institute of Biochemistry, Eidgenossische Technische Hochschule Zurich (ETHZ), Zurich, Switzerland
Abstract
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.
Citation: Farnung BO, Brun CM, Arora R, L
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