Human telomerase acts as a hTR-independent reverse transcriptase in mitochondria.

TitleHuman telomerase acts as a hTR-independent reverse transcriptase in mitochondria.
Publication TypeJournal Article
Year of Publication2012
AuthorsSharma, NK, Reyes, A, Green, P, Caron, MJ, Bonini, MG, Gordon, DM, Holt, IJ, Santos, JHertzog
JournalNucleic Acids Res
Volume40
Issue2
Pagination712-25
Date Published2012 Jan
ISSN1362-4962
KeywordsCells, Cultured, DNA, Mitochondrial, Humans, Membrane Potential, Mitochondrial, Mitochondria, Protein Transport, Reverse Transcription, RNA, RNA, Mitochondrial, RNA, Transfer, Telomerase
Abstract

Human 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.

DOI10.1093/nar/gkr758
Alternate JournalNucleic Acids Res.
Citation Key10.1093/nar/gkr758
PubMed ID21937513
PubMed Central IDPMC3258147
Grant ListMC_U105663140 / / Medical Research Council / United Kingdom