The nucleolar localization domain of the catalytic subunit of human telomerase

Katherine T. Etheridge, Soma S.R. Banik, Blaine N. Armbruster, Yusheng Zhu, Rebecca M. Terns, Michael P. Terns, Christopher M. Counter

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

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 sub-units to the nucleolus supports the premise that the assembly of telomerase occurs in the nucleolus.

Original languageEnglish (US)
Pages (from-to)24764-24770
Number of pages7
JournalJournal of Biological Chemistry
Volume277
Issue number27
DOIs
StatePublished - Jul 5 2002

Fingerprint

Telomerase
Enzymes
Cell Nucleolus
telomerase RNA
Mutation
Ribonucleoproteins
RNA-Binding Proteins
Chromosomes
DNA Replication
Ribosomes
Substitution reactions
Association reactions
RNA
DNA

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Etheridge, K. T., Banik, S. S. R., Armbruster, B. N., Zhu, Y., Terns, R. M., Terns, M. P., & Counter, C. M. (2002). The nucleolar localization domain of the catalytic subunit of human telomerase. Journal of Biological Chemistry, 277(27), 24764-24770. https://doi.org/10.1074/jbc.M201227200
Etheridge, Katherine T. ; Banik, Soma S.R. ; Armbruster, Blaine N. ; Zhu, Yusheng ; Terns, Rebecca M. ; Terns, Michael P. ; Counter, Christopher M. / The nucleolar localization domain of the catalytic subunit of human telomerase. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 27. pp. 24764-24770.
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Etheridge, KT, Banik, SSR, Armbruster, BN, Zhu, Y, Terns, RM, Terns, MP & Counter, CM 2002, 'The nucleolar localization domain of the catalytic subunit of human telomerase', Journal of Biological Chemistry, vol. 277, no. 27, pp. 24764-24770. https://doi.org/10.1074/jbc.M201227200

The nucleolar localization domain of the catalytic subunit of human telomerase. / Etheridge, Katherine T.; Banik, Soma S.R.; Armbruster, Blaine N.; Zhu, Yusheng; Terns, Rebecca M.; Terns, Michael P.; Counter, Christopher M.

In: Journal of Biological Chemistry, Vol. 277, No. 27, 05.07.2002, p. 24764-24770.

Research output: Contribution to journalArticle

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T1 - The nucleolar localization domain of the catalytic subunit of human telomerase

AU - Etheridge, Katherine T.

AU - Banik, Soma S.R.

AU - Armbruster, Blaine N.

AU - Zhu, Yusheng

AU - Terns, Rebecca M.

AU - Terns, Michael P.

AU - Counter, Christopher M.

PY - 2002/7/5

Y1 - 2002/7/5

N2 - 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 sub-units to the nucleolus supports the premise that the assembly of telomerase occurs in the nucleolus.

AB - 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 sub-units to the nucleolus supports the premise that the assembly of telomerase occurs in the nucleolus.

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