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Telomere-independent functions of telomerase in nuclei, cytoplasm, and mitochondria

Ilaria Chiodi and Chiara Mondello*

Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, Pavia, Italy
Telomerase canonical activity at telomeres prevents telomere shortening, allowing chromosome stability and cellular proliferation. To perform this task, the catalytic subunit (telomerase reverse transcriptase, TERT) of the enzyme works as a reverse transcriptase together with the telomerase RNA component (TERC), adding telomeric repeats to DNA molecule ends. Growing evidence indicates that, besides the telomeric-DNA synthesis activity, TERT has additional functions in tumor development and is involved in many different biological processes, among which cellular proliferation, gene expression regulation, and mitochondrial functionality. TERT has been shown to act independently of TERC in the Wnt-β-catenin signaling pathway, regulating the expression of Wnt target genes, which play a role in development and tumorigenesis. Moreover, TERT RNA-dependent RNA polymerase activity has been found, leading to the genesis of double-stranded RNAs that act as precursor of silencing RNAs. In mitochondria, a TERT TERC-independent reverse transcriptase activity has been described that could play a role in the protection of mitochondrial integrity. In this review, we will discuss some of the extra-telomeric functions of telomerase.
Keywords: telomerase, TERT, telomere, transformation, cancer, apoptosis, mitochondria, RNA interference
Citation: Chiodi I and Mondello C (2012) Telomere-independent functions of telomerase in nuclei, cytoplasm, and mitochondria. Front. Oncol. 2:133. doi: 10.3389/fonc.2012.00133
Received: 31 July 2012; Accepted: 18 September 2012;
Published online: 28 September 2012.
Edited by:
Claus M. Azzalin, Eidgenössische Technische Hochschule Zürich, Switzerland
Susan M. Bailey, Colorado State University, USA
Reviewed by:
Xu-Dong Zhu, McMaster University, Canada
Yongmei Song, Chinese Academy of Medical Sciences and Peking Union Medical College, China
Copyright: © 2012 Chiodi and Mondello. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
*Correspondence: Chiara Mondello, Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, Via Abbiategrasso 207, 27100 Pavia, Italy. e-mail: