The nucleolar localization domain of the catalytic subunit of human telomerase.

Published

Journal Article

Telomerase is the enzyme essential to complete the replication of the terminal DNA of most eukaryotic chromosomes. In humans, this enzyme is composed of the telomerase reverse transcriptase (hTERT) and telomerase RNA (hTR) subunits. hTR has been found in the nucleolus, a site of assembly of ribosomes as well as other ribonucleoproteins (RNPs). We therefore tested whether the hTERT component is also found in the nucleolus, where it could complex with the hTR RNA to form a functional enzyme. We report here that hTERT does indeed localize to the nucleolus, and we mapped the domain responsible for this localization to the hTR-binding region of the protein by deletion analysis. Substitution mutations in two of the three conserved hTR-binding domains in this nucleolar localization domain (NoLD) abolished nucleolar localization. However, another mutation that impeded hTR binding did not alter this subcellular localization. Additionally, wild type hTERT was detected in the nucleolus of cells that failed to express hTR. Taken together, we propose that the nucleolar localization of hTERT involves more than just the association with the hTR subunit. Furthermore, the coincidental targeting of both the hTR and hTERT subunits to the nucleolus supports the premise that the assembly of telomerase occurs in the nucleolus.

Full Text

Duke Authors

Cited Authors

  • Etheridge, KT; Banik, SSR; Armbruster, BN; Zhu, Y; Terns, RM; Terns, MP; Counter, CM

Published Date

  • July 5, 2002

Published In

Volume / Issue

  • 277 / 27

Start / End Page

  • 24764 - 24770

PubMed ID

  • 11956201

Pubmed Central ID

  • 11956201

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.M201227200

Language

  • eng

Conference Location

  • United States