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dc.contributor.authorSharma, Nilesh K.
dc.contributor.authorReyes, Aurelio
dc.contributor.authorGreen, Paula
dc.contributor.authorCaron, Matthieu J.
dc.contributor.authorBonini, Marcelo G.
dc.contributor.authorGordon, Donna M.
dc.contributor.authorHolt, Ian J.
dc.contributor.authorSantos, Janine Hertzog
dc.date.accessioned2012-03-16T13:38:14Z
dc.date.available2012-03-16T13:38:14Z
dc.date.issued2011-09
dc.identifier.bibliographicCitationSharma, N. K., Reyes, A., Green, P., Caron, M. J., Bonini, M. G., Gordon, D. M., Holt, I. J., & Santos, J. H. 2011. Human telomerase acts as a hTR-independent reverse transcriptase in mitochondria. Nucleic Acids Research. 2012. Vol. 40, No. 2, 712-725. doi:10.1093/nar/gkr75en
dc.identifier.issn0305-1048
dc.identifier.issn1362-4962
dc.identifier.otherDOI:10.1093/nar/gkr758
dc.identifier.urihttp://hdl.handle.net/10027/8213
dc.descriptionThe Author(s) 2011. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.en
dc.description.abstractHuman telomerase reverse transcriptase (hTERT) is localized to mitochondria, as well as the nucleus, but details about its biology and function in the organelle remain largely unknown. Here we show, using multiple approaches, that mammalian TERT is mitochondrial, co-purifying with mitochondrial nucleoids and tRNAs. We demonstrate the canonical nuclear RNA [human telomerase RNA (hTR)] is not present in human mitochondria and not required for the mitochondrial effects of telomerase, which nevertheless rely on reverse transcriptase (RT) activity. Using RNA immunoprecipitations from whole cell and in organello, we show that hTERT binds various mitochondrial RNAs, suggesting that RT activity in the organelle is reconstituted with mitochondrial RNAs. In support of this conclusion, TERT drives first strand cDNA synthesis in vitro in the absence of hTR. Finally, we demonstrate that absence of hTERT specifically in mitochondria with maintenance of its nuclear function negatively impacts the organelle. Our data indicate that mitochondrial hTERT works as a hTR-independent reverse transcriptase, and highlight that nuclear and mitochondrial telomerases have different cellular functions. The implications of these findings to both the mitochondrial and telomerase fields are discussed.en
dc.description.sponsorshipFunding for open access charge: Department of Defense, Army Research Office (grant number 56027LS, to J.H.S.). Conflict of interest statement: None declared.en
dc.language.isoen_USen
dc.publisherOxford University Pressen
dc.titleHuman telomerase acts as a hTR-independent reverse transcriptase in mitochondriaen
dc.typeArticleen


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