title: Human telomerase acts as a hTR-independent reverse transcriptase in mitochondria.
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.
authors.affiliation: Department of Pharmacology and Physiology, New Jersey Medical School of UMDNJ, 185 South Orange Avenue, Medical Sciences Building, Newark, NJ 07103, USA.
authors.forename: Nilesh K
authors.initials: NK
authors.lastname: Sharma
authors.forename: Aurelio
authors.initials: A
authors.lastname: Reyes
authors.forename: Paula
authors.initials: P
authors.lastname: Green
authors.forename: Matthieu J
authors.initials: MJ
authors.lastname: Caron
authors.forename: Marcelo G
authors.initials: MG
authors.lastname: Bonini
authors.forename: Donna M
authors.initials: DM
authors.lastname: Gordon
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Holt
authors.forename: Janine Hertzog
authors.initials: JH
authors.lastname: Santos
mesh_terms: D002478:Cells, Cultured; D004272:DNA, Mitochondrial / Q000302:isolation & purification; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000201:enzymology* / Q000648:ultrastructure; D021381:Protein Transport; D012313:RNA / Q000302:isolation & purification / Q000378:metabolism; D000077278:RNA, Mitochondrial; D012343:RNA, Transfer / Q000302:isolation & purification; D048348:Reverse Transcription; D019098:Telomerase / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D004272:DNA, Mitochondrial; D000077278:RNA, Mitochondrial; C422952:telomerase RNA; D012313:RNA; D012343:RNA, Transfer; D019098:Telomerase