Catalytically active telomerase holoenzyme is assembled in the dense fibrillar component of the nucleolus during S phase

Ji Hoon Lee, Yang Sin Lee, Sun Ah Jeong, Prabhat Khadka, Jürgen Roth, In Kwon Chung

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The maintenance of human telomeres requires the ribonucleoprotein enzyme telomerase, which is composed of telomerase reverse transcriptase (TERT), telomerase RNA component, and several additional proteins for assembly and activity. Telomere elongation by telomerase in human cancer cells involves multiple steps including telomerase RNA biogenesis, holoenzyme assembly, intranuclear trafficking, and telomerase recruitment to telomeres. Although telomerase has been shown to accumulate in Cajal bodies for association with telomeric chromatin, it is unclear where and how the assembly and trafficking of catalytically active telomerase is regulated in the context of nuclear architecture. Here, we show that the catalytically active holoenzyme is initially assembled in the dense fibrillar component of the nucleolus during S phase. The telomerase RNP is retained in nucleoli through the interaction of hTERT with nucleolin, a major nucleolar phosphoprotein. Upon association with TCAB1 in S phase, the telomerase RNP is transported from nucleoli to Cajal bodies, suggesting that TCAB1 acts as an S-phase-specific holoenzyme component. Furthermore, depletion of TCAB1 caused an increase in the amount of telomerase RNP associated with nucleolin. These results suggest that the TCAB1-dependent trafficking of telomerase to Cajal bodies occurs in a step separate from the holoenzyme assembly in nucleoli. Thus, we propose that the dense fibrillar component is the provider of active telomerase RNP for supporting the continued proliferation of cancer and stem cells.

Original languageEnglish
Pages (from-to)137-152
Number of pages16
JournalHistochemistry and cell biology
Volume141
Issue number2
DOIs
Publication statusPublished - 2014 Feb

All Science Journal Classification (ASJC) codes

  • Histology
  • Molecular Biology
  • Medical Laboratory Technology
  • Cell Biology

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