title: Importin 7 and Nup358 promote nuclear import of the protein component of human telomerase.
abstract: In actively dividing eukaryotic cells, chromosome ends (telomeres) are subject to progressive shortening, unless they are maintained by the action of telomerase, a dedicated enzyme that adds DNA sequence repeats to chromosomal 3'end. For its enzymatic function on telomeres, telomerase requires nuclear import of its protein component (hTERT in human cells) and assembly with the RNA component, TERC. We now confirm a major nuclear localization signal (NLS) in the N-terminal region of hTERT and describe a novel one in the C-terminal part. Using an siRNA approach to deplete several import receptors, we identify importin 7 as a soluble nuclear transport factor that is required for efficient import. At the level of the nuclear pore complex (NPC), Nup358, a nucleoporin that forms the cytoplasmic filaments of the NPC, plays an important role in nuclear import of hTERT. A structure-function analysis of Nup358 revealed that the zinc finger region of the nucleoporin is of particular importance for transport of hTERT. Together, our study sheds light on the nuclear import pathway of hTERT.
authors.affiliation: Institute of Molecular Biology, Faculty of Medicine, University of Göttingen, Göttingen, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Frohnert
authors.affiliation: Institute of Molecular Biology, Faculty of Medicine, University of Göttingen, Göttingen, Germany.
authors.forename: Saskia
authors.initials: S
authors.lastname: Hutten
authors.affiliation: Institute of Molecular Biology, Faculty of Medicine, University of Göttingen, Göttingen, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Wälde
authors.affiliation: Institute of Molecular Biology, Faculty of Medicine, University of Göttingen, Göttingen, Germany.
authors.forename: Annegret
authors.initials: A
authors.lastname: Nath
authors.affiliation: Institute of Molecular Biology, Faculty of Medicine, University of Göttingen, Göttingen, Germany.
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Kehlenbach
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D028884:Karyopherins / Q000378:metabolism*; D018832:Molecular Chaperones / Q000378:metabolism*; D019913:Nuclear Localization Signals / Q000235:genetics*; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D019098:Telomerase / Q000378:metabolism*
chemical_list: C466996:IPO7 protein, human; D028884:Karyopherins; D018832:Molecular Chaperones; D019913:Nuclear Localization Signals; D028861:Nuclear Pore Complex Proteins; D034741:RNA, Small Interfering; D018160:Receptors, Cytoplasmic and Nuclear; C094493:ran-binding protein 2; D019098:Telomerase