Histochemistry and Cell Biology

, Volume 141, Issue 2, pp 137–152 | Cite as

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 RothEmail author
  • In Kwon ChungEmail author
Original Paper


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.


Telomere Telomerase holoenzyme assembly Dense fibrillar component of nucleolus hTERT TCAB1 Cajal body 



This work was supported by World Class University Fund from the Korean Ministry of Education, Science, and Technology R31-2009-000-10086-0 to IKC and JR.

Supplementary material

418_2013_1166_MOESM1_ESM.pdf (1.4 mb)
Supplementary material 1 (PDF 1399 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Department of Integrated Omics for Biomedical ScienceGraduate School of Yonsei UniversitySeoulKorea
  2. 2.Department of Systems Biology, College of Life Science and BiotechnologyYonsei UniversitySeoulKorea

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