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Importin 7 and Nup358 Promote Nuclear Import of the Protein Component of Human Telomerase

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 nucle...

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Autores principales: Frohnert, Cornelia, Hutten, Saskia, Wälde, Sarah, Nath, Annegret, Kehlenbach, Ralph H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3930611/
https://www.ncbi.nlm.nih.gov/pubmed/24586428
http://dx.doi.org/10.1371/journal.pone.0088887
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author Frohnert, Cornelia
Hutten, Saskia
Wälde, Sarah
Nath, Annegret
Kehlenbach, Ralph H.
author_facet Frohnert, Cornelia
Hutten, Saskia
Wälde, Sarah
Nath, Annegret
Kehlenbach, Ralph H.
author_sort Frohnert, Cornelia
collection PubMed
description 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.
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spelling pubmed-39306112014-02-25 Importin 7 and Nup358 Promote Nuclear Import of the Protein Component of Human Telomerase Frohnert, Cornelia Hutten, Saskia Wälde, Sarah Nath, Annegret Kehlenbach, Ralph H. PLoS One Research Article 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. Public Library of Science 2014-02-20 /pmc/articles/PMC3930611/ /pubmed/24586428 http://dx.doi.org/10.1371/journal.pone.0088887 Text en © 2014 Frohnert et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Frohnert, Cornelia
Hutten, Saskia
Wälde, Sarah
Nath, Annegret
Kehlenbach, Ralph H.
Importin 7 and Nup358 Promote Nuclear Import of the Protein Component of Human Telomerase
title Importin 7 and Nup358 Promote Nuclear Import of the Protein Component of Human Telomerase
title_full Importin 7 and Nup358 Promote Nuclear Import of the Protein Component of Human Telomerase
title_fullStr Importin 7 and Nup358 Promote Nuclear Import of the Protein Component of Human Telomerase
title_full_unstemmed Importin 7 and Nup358 Promote Nuclear Import of the Protein Component of Human Telomerase
title_short Importin 7 and Nup358 Promote Nuclear Import of the Protein Component of Human Telomerase
title_sort importin 7 and nup358 promote nuclear import of the protein component of human telomerase
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3930611/
https://www.ncbi.nlm.nih.gov/pubmed/24586428
http://dx.doi.org/10.1371/journal.pone.0088887
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